But it's not their first rodeo together: The pair previously costarred in the 2011 comedy Just Go With It, which became a box office hit despite pans from critics (stop us if you've heard that before with a Sandler movie).
Aniston, 50, and Sandler, 52, have been good friends ever since, so the reunion was a no-brainer.
"We hung out very well together back then, we said 'Let's give it another shot,'" Sandler tells Yahoo Entertainment (watch above). "We love each other."
They were "determined" to reunite, Aniston says.
The pair play a married New York couple (he's a cop, she's a hairdresser) who take a long-delayed honeymoon to the French Riviera, only to be caught up in the murder of a billionaire business tycoon on the yacht they've boarded with his eccentric family members-turned-suspects.
Early scenes with Aniston styling the hair of other women ring a bit ironic, given America's long obsession with the actress's own hairstyles. So was that an intentional wink?
"No!" Aniston insists, to which Sandler disagrees: "Yes, it is a wink," he says.
And speaking of Aniston's hair, how does she now look back on "The Rachel," the 'do made famous in Friends that was mimicked by women (and some men, like Sandler in Little Nicky) all over the world?
"It was a great haircut, loved it, fond memories of it," Aniston says. "But everyone's interpretation of 'The Rachel' was a little different."
The self-aware funnywoman catches herself.
"It's so silly to say 'The Rachel.'"
Murder Mystery is now streaming on Netflix. Watch the trailer:
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