"With tremendous love and respect for each other, and the 18 years we spent together as a couple, we have made the decision to separate," Stiller and Taylor said. "Our priority will continue to be raising our children as devoted parents and the closest of friends. We kindly ask that the media respect our privacy at this time."
The couple, who met while filming a never-broadcast TV pilot called Heat Vision and Jack, tied the knot in May 2000 at an oceanfront ceremony in Kauai, Hawaii. "When I met her, I pretty much thought, 'That's the person,'" Stiller told ET in a 2007 interview. "It was like, 'Wow, this is a great person. I love her.'" The two welcomed daughter Ella Olivia in April 2002 and son Quinlin Dempsey in July 2005.
Throughout their marriage, Stiller, 51, and Taylor, 45, continued to share the screen -- in projects like Zoolander, Dodgeball: A True Underdog Story, Tropic Thunder, Arrested Development and most recently, Zoolander 2.
ET caught up with the couple at Zoolander 2's premiere last February, where they opened up about how working together affected their then 15-year marriage.
"It's the best. I mean, I think that, you know, the reality is there's such an unspoken connection," Taylor shared. "I feel like for us, when we first met, it was on set... He's amazing."
"[Having a] sense of humor [is the secret to our marriage]," she continued. "I have to say, sense of humor is the greatest thing."
"I say that's the secret to a happy marriage anywhere in any city, not just Hollywood," Stiller agreed. "I think you got to laugh, because after a while, you know, life is life. We all have to deal with what life throws at us, so you got to have a sense of humor about it. If you can share that, at the end, it makes a huge difference."
"It came out of the blue for me. I had no idea," Stiller, now cancer-free, said during a radio interview with Howard Stern. "At first, I didn't know what was gonna happen. I was scared. It just stopped everything in your life because you can't plan for a movie because you don't know what's gonna happen."
"As I learned more about my disease (one of the key learnings is not to Google 'people who died of prostate cancer' immediately after being diagnosed with prostate cancer), I was able to wrap my head around the fact that I was incredibly fortunate," he wrote in a blog post. "Fortunate because my cancer was detected early enough to treat. And also because my internist gave me a test he didn't have to."