Angelina Jolie has filed for divorce from Brad Pitt for "the health of her family", two years after the couple wed at their French estate Chateau Miraval.
The actress filed papers on Monday citing irreconcilable differences as the reason for the split and asking for physical custody of the couple's six children.
A source close to the couple told TMZ that Jolie, 41, made the decision to file because of the way "Brad was parenting the children", adding that "she was extremely upset with his methods".
Read more: Five big celebrity break-ups
That same source claims Jolie became "fed up" with Pitt's consumption of "weed and possibly alcohol" mixed with his "anger problem".
The pair began dating in early 2005 after they met on the set of Mr and Mrs Smith.
Page Six is reporting however that it was after Jolie learned through a private eye that Pitt was cheating on her with Marion Cotillard on the set of their new film Allied that she made the decision to split from the actor.
Cotillard has been in a relationship with actor and writer Guillaume Canet since 2007, and the couple have a 4-year-old son.
Pitt said in a statement to DailyMail.com: "I am very saddened by this, but what matters most now is the well-being of our kids. I kindly ask the press to give them the space they deserve during this challenging time."
Jolie, who is being represented by Laura Wasser, is not asking for spousal support in the divorce.
Wasser most recently represented Johnny Depp in his divorce from Amber Heard.
Jolie has listed the separation date as September 15, 2016, just last Thursday.
The couple had not been seen together in months and were last photographed on a red carpet together in November last year while promoting their film By The Sea.
An attorney for Jolie, Robert Offer, said yesterday that she has filed for the dissolution of the marriage "for the health of the family".
He then added: "She will not be commenting, and asks that the family be given its privacy at this time."
Jolie's manager Geyer Kosinski also released a statement, saying: 'Angelina will always do what's in the best interest to protect her children.
"She appreciates everyone's understanding of their need for privacy at this time."
Pitt and Cottilard have yet to respond to a request for comment from DailyMail.com.
"I could say the divorce announcement is a shock, but it's not," a long-time friend of Brad and Angelina told DailyMail.com.
"This divorce deal has been brewing for a long time."
The friend said it wasn't long after the couple tied the knot in 2014 that cracks began to show in their 12-year relationship.
"When Angelina underwent her mastectomy in 2013, her health and life in general became a priority for her," added the source.
"Her views on life changed. Suddenly she saw herself walking in her late mother's shoes - and she was no longer that wild, fun-loving woman she used to be, she was taking things a lot more seriously.
Her mum, Marcheline Bertrand, who died of ovarian cancer in 2007, had always been Angelina's biggest influence, friends say.
"Brad was supportive, and wanted to be there for her, so they decided to marry - more for the sake of their six children than themselves. They wanted the kids to have the security of knowing their parents were committed because they had been very affected by the their mom's ill health."
But it was not long after the wedding, that things began to change for the couple.
"Angelina wasn't into wasting time on frivolous things. Brad felt it was important for them to live life to the fullest, but as the months passed, Angelina seemed to withdraw, making the children and her work with the UN a priority.
"Angelina wasn't really interested in doing any project that took her away from the children and home, but Brad was still wanting the wanderlust, adventure-filled life that first attracted him to her."
Document courtesy of TMZ
The friend said that the underlying reasons behind the Pitt-Jolie split are the same that caused him to divorce Jennifer Aniston - "he was bored stiff with the sedate, quiet lifestyle they were leading".
"When he was with Jennifer, it was Angelina who provided the excitement that was missing in his life. But when Angelina shifted gears and became more serious - that wasn't what Brad thought he was buying into."
Pitt also wanted to continue tinkering with building work on Chateau Miraval, their sprawling home in the south of France, but Jolie was content with it as it was and "wanted to just sit back and enjoy the life they had created".
And Pitt had thrown himself back into acting, with six projects since their marriage. He is also about to start on a sequel to World War Z, which will again take him away from his wife and children
"Angelina did not approve of this movie because she knew it would once again take him away from her and the family when she felt they needed to spend more time together," said the friend.
Pitt, who dabbles in architecture - he designed more than 100 homes in New Orleans after Hurricane Katrina - had also signed papers to start work on a $1.5 billion resort project in Croatia. "He's a huge part of the planning. He can't wait to get started," said the friend.
The Croatia project allowed him to meet some of the world's leading architects and learn from them, said the friend. Pitt traveled to Zablace on the Dalmatian coast this month.
"For the past year Brad and Angelina have been leading separate lives. He's always flying off to one place or another, while she stays home with the kids. With each month that passed, Brad and Angelina grew further apart," said the source, "Friends have been predicting a divorce was on the horizon.
"Now it's come to pass, and it's no surprise."
This will be the third divorce for Jolie, who was previously married to Elementary star Johnny Lee Miller for three years after the pair met on the set of the film Hackers.
She later wed Billy Bob Thornton just two months after the pair began dating when they met on the set of Pushing Tin.
Thornton had been engaged to actress Laura Dern at the time.
Pitt's first marriage to actress Jennifer Aniston ended in 2005, with rumours swirling at the time that it was because of his relationship with Jolie, whom he met when the two worked on the 2005 film Mr and Mrs Smith.
The split comes less than a year after the two released By the Sea, which told the story of an unhappily married couple.
Jolie directed and starred in the film alongside Pitt, and admitted how difficult the shoot was at times.
"It was our way of testing ourselves. We knew that if we could get through this, we'd come out even stronger and happier. And we did," she said of making the film.
"We've always liked putting ourselves through challenges, even though it was maybe a little more dangerous for us as a couple."
She then added: "I don't think we want to go through it again though."
Jolie also said in an interview with the Telegraph while promoting the film: "To be clear: we have fights and problems like any other couple. We have days when we drive each other absolutely mad and want space, but the problems in the movie aren't our specific problems."
In another interview Jolie said of the unhappy couple at the centre of the film, played by herself and Pitt: "It almost makes you get past those issues because you can laugh at them.
"You do a film about bad marriage and you witness that behaviour. You study it, you let it out, you attack each other and then you just want to hold each other and make sure you never behave that way."
The two also said that filming the movie on Malta served as their honeymoon.
Jolie adopted her first son Maddox in March 2002, two years before she met Pitt on Mr and Mrs Smith.
The film was originally set to star Nicole Kidman, but the actress dropped out at the last second.
The couple denied that they were together, even after US Weekly ran photos in August 2005 of the two playing with Maddox at their rented villa on Diani Beach, Kenya.
It was later revealed that Pitt, 52, had been by Jolie's side one month before when she adopted daughter Zahara from a orphanage in Ethiopia.
Soon after this is when Pitt formally adopted Jolie's son Maddox, and the children changed their surname to Jolie-Pitt.
The pair finally announced they were together in 2006 after Jolie became pregnant with Pitt's child.
Shiloh Jolie-Pitt was born in May 2006 in Namibia, where the couple chose to give birth to avoid a press frenzy.
The following March the couple adopted again, this time travelling to Vietnam and adding 3-year-old Pax Thien to the family.
Jolie then became pregnant once more, confirming in May 2008 that the couple were expecting twins.
Knox and Vivienne were born in July of that year. The first photos of the two sold for an astounding $14 million in a deal between Hello and People.
The two held off on getting married however, but said in interviews that their six children wanted them to tie the knot.
They finally revealed that they were engaged in April 2012, and were married a little over two years later in August 2014.
During that time, Jolie secretly underwent a double mastectomy in February 2013 after discovering she had a defective BRCA-1 gene that put her at high risk of developing breast and ovarian cancers.
Jolie had her ovaries removed in early 2015, something she spoke about last November with NBC's Tom Brokaw in her first joint interview with Pitt in more than a decade.
Read more: Five of Hollywood's most enduring marriages
In that interview, Jolie praised Pitt for his support while she underwent the two procedures.
"I knew through the surgeries that he was on my side and that this wasn't something where I was going to feel less of a woman, because my husband wasn't going to let that happen," said Jolie.
Pitt meanwhile said he would do "whatever's got to be done to keep the family together, and keep the family together as long as possible is going to be done".
He then added: "This was her charge, no question. It's a scary decision. There's many things that can go wrong and go many different directions."
The couple's wedding took place at Chateau Miraval, their home in France.
The secret ceremony featured only their six children, and Jolie wore a custom Versace dress, which featured drawings by her sons and daughters.
Jolie's actor father Jon Voight spoke about his daughter's high-profile split in an interview with Inside Edition yesterday.
"It's very sad. Something very serious must have happened for Angelina to make a decision like this," said Voight.
He then added: "I am concerned for Angie and the children, and hopefully I'll be seeing them very soon."
A source close to Pitt told the Sun: "There have been rumours around the status of the relationship for years, but they are now very much in turmoil and it is hard to see a way out."
The source went on to say: "There have been a constant string of arguments about their future and their children.
"The marriage is in crisis and friends doubt it will survive, although Brad and Angelina are both committed to do as much as they can to stay together for the sake of the kids while they are still young.
"They have come through a lot before and somehow managed to keep up appearances but Brad thinks this time is different."
May 2004: Although Pitt is married to Jennifer Aniston, rumours of an on-set romance swirl after Pitt and Jolie start filming Mr & Mrs Smith.
January 2005: Pitt and Aniston announce in a joint statement that after "much thoughtful consideration" they had decided to split. They add: "We happily remain committed and caring friends with great love and admiration for one another."
March 2005: Aniston files for divorce citing "irreconcilable differences" as speculation about Pitt and Jolie's romance continued.
April 2005: Pitt and Jolie's relationship is confirmed after paparazzi photographs of them on holiday in Kenya with her son Maddox surface. They have yet to speak publicly about it.
July 2005: Aniston is reportedly left heartbroken when Pitt and Jolie take part in a revealing photoshoot for W magazine entitled Domestic Bliss. The photo essay shows them as a couple with children. Later that month Angelina adopts her second child, daughter Zahara, from Ethiopia.
September 2005: Aniston slams Pitt as having a "sensitivity chip missing" following the W photo shoot, which he brainstormed.
October 2005: Pitt and Aniston's divorce is finalised.
January 2006: Jolie and Pitt announce she is pregnant with their first child and Pitt applies to formally adopt her children Maddox and Zahara.
May 2006: The couple's first biological child Shiloh Nouvel Jolie-Pitt is born in Swakopmund, Namibia.
December 2006: Jolie tells Vogue that while filming Mr & Mrs Smith, she couldn't "wait to get to work" to see Pitt. Two years later, Aniston brands the comments "uncool".
March 2007: Jolie adopts 3-year-old Pax Thien from Vietnam.
May 2008: At the Cannes Film Festival, Jolie confirms she is expecting twins. Knox Leon and Vivienne Marcheline are born in July.
October 2008: Jolie reveals her romance with Pitt began while he was married to Aniston as she says they '"fell in love" on the set of Mr & Mrs Smith. The pair had always maintained up until this point that their relationship only started after he split from Aniston.
September 2011: Pitt tells Parade magazine that before Jolie he "wasn't living an interesting life". He added: "I think that my marriage had something to do with it. Trying to pretend the marriage was something that it wasn't." He said he's finally a "satisfied man" with Jolie. He later insisted the comments were misunderstood, adding: "Jen is an incredibly giving, loving, and hilarious woman who remains my friend."
December 2011/January 2012: The couple admit in separate interviews that the children are encouraging them to marry. While they had planned to wait until gay marriage was legal, they reveal the pressure from the children is strong.
April 2012: Pitt and Jolie reveal their engagement.
February 2013: Jolie has a secret double mastectomy after discovering she had a defective BRCA-1 gene that put her at high risk of developing breast and ovarian cancers. She tells the world about it in a New York Times op-ed in May.
July 2014: It is announced that Pitt and Jolie will reunite on the big screen for the first time since Mr & Mrs Smith. Jolie will write and direct the "intimate, character-driven drama" By the Sea.
August 2014: The couple tie the knot in a secret ceremony at Chateau Miraval in France and after a short family honeymoon in Nice, the Jolie-Pitts head to Malta to start shooting By The Sea.
September 2016: Jolie files for divorce citing irreconcilable differences.
Dolly Parton will receive the Jean Hersholt Humanitarian Award for her charity work.