And it has been claimed that the stresses they have faced eventually took their toll on the couple’s relationship.
'Catherine and Michael are taking some time apart to evaluate and work on their marriage. There will be no further comment,' a representative told MailOnline on behalf of the pair.
'Taking time apart': Michael Douglas and Catherine Zeta-Jones, pictured at the Oscars in February, have separated after 13 years of marriage
In August 2010 Michael revealed he was suffering from stage IV throat cancer, and after undergoing treatment the actor stated the following January that the tumour was gone.
At the time, he attributed the illness to stress, his previous alcohol abuse and years of heavy smoking.
But in June this year he made comments saying the HPV virus - which is contracted through oral sex - could have been the cause of his cancer.
Tough times: The couple's struggles, including Michael's cancer battle, have apparently taken their toll. Michael in pictured here in April 2011 after recovering from throat cancer
Embarrassed: Catherine was reportedly humiliated after Michael claimed on Graham Norton in April that the HPV virus, which is contracted from oral sex, caused his cancer and didn't clarify it was before he met her
It has been claimed that this was the tipping point and a source told the publication: ‘Things went downhill from there.’
Michael revealed in a separate interview when Catherine was coming home from receiving treatment, which annoyed the Chicago actress as she wanted this to remain private, the magazine reports.
But the couple stuck by each other through their respective illnesses and Michael gushed at the time of his cancer that his better half had been ‘wonderfully supportive’.
Facing her demons: Catherine has received treatment twice for bipolar disorder and spoke about her ordeal on Ellen in January
Miles apart: The couple were last seen publicly on April 22 and Michael is currently in France while Catherine remains in New York
In 2011, Michael said: ‘I’m very proud of Catherine for doing something positive about her situation.’
Michael, 68, and Catherine, 43, have two children together: son Dylan, 13, and 10-year-old daughter Carys, and family life has been rather a bumpy ride.
Michael also has 34-year-old son Cameron from his previous marriage to Diandra Luker, who currently serving time in jail for possessing heroin and dealing large amounts of methamphetamine and cocaine.
He was sentenced in 2010 and a year and a half later, found guilty of possessing drugs in prison, so had his sentence extended.
Brave face: Michael was seen heading out for a solo dinner while on holiday in Nice on Tuesday
Loyal supporters: Michael took his mind off the separation by greeting fellow diners at La Petite Maison
While Michael blamed himself for ‘being a bad father’, he admitted jail is the best place for his son.
‘Look, my son was a drug dealer, and he’s been trying to kill himself for a while,’ the star admitted on The Today Show in 2010 after the sentencing. ‘I can’t condone his behaviour.
‘I think the court recognised his drug addiction as well as the crime that he committed and it's an adequate, I think, amount of time for anybody to spend in jail. And the best part of it is, he will be able to start his life afresh.’
The family: Michael and Catherine have two children together, son Dylan, now 13, and Carys, 10, who they are pictured with at Buckingham Palace in February 2011
The Behind The Candelabra star has also not had the easiest time with son Dylan, who has learning difficulties.
‘My son deals with dyslexia to a degree — it runs in the family and my brother has it,’ Michael revealed in 2010. ‘He goes to a special school.’
And the star admitted at the time that he was relishing focusing on his duties as a father.
‘I’m not driven like I once was — these days I am consumed with being a father and with my responsibilities as a husband,’ he added to The Guardian. ‘I never anticipated starting a family at my age. I’m genuinely happy to let Catherine work, while I stay at home with the children. I cherish this time.’
Incarcerated: Michael's eldest son Cameron from a previous marriage will be behind bars until early 2018
Blaming himself: Michael believes he was 'a bad father' to Cameron, who is serving time for drug possession and dealing. Here the pair are seen in April 2009, one year before he was sentenced
Two years later the couple married in a lavish ceremony at the Plaza Hotel in Manhattan, which was attended by the likes of Jack Nicholson and Martha Stewart.
The Hollywood power couple are currently thousands of miles apart, with Michael holidaying in France solo while Catherine remains in New York.
According to People neither of the two, who were last seen publicly together on April 22, are making moves towards a divorce or legal separation at this stage.
Young love: The couple are seen here in March 2000, eight months before their lavish New York wedding