The story revolves around a couple whose brief adulterous affair lands them in more trouble than they bargained for.
"There's definitely an element of fatal attraction here. I think that's great; that's a compliment," the former "Friends" superstar told FOX News.
"A terrible thing happens and it's a nightmare that begins and just seems to spiral out of control," co-star Clive Owen added.
But don't expect your average tale of suspense. Even the cast was surprised by how the story works out.
"I never saw it coming. You know, you very often read a thriller and you can see where it's heading or things are spelled out too clearly or they're so clever in their twist and turns that it's all a bit contrived and you really don't buy the situation," Owen said.
Said Aniston: "I really kind of pride myself on figuring stuff out pretty quickly [but] I couldn't, couldn't. I just had no idea."
With the exposure — or overexposure — of her personal life, it's easy to forget "Derailed" is Aniston's first film since "Friends."
The 36-year-old actress, whom tabloids long ago nicknamed "America's Sweetheart," is starting a strong push for big-screen stardom with four upcoming releases that include "The Break Up," "Rumor Has It" and "Friends With Money."
"I'm not trying to shed any labels," she said of moving away from her "Rachel Green" character but acknowledges "a big part" of the appeal of "Derailed" was its difference from her previous roles.
Aniston did do films on the side during "Friends" — "The Object of My Affection," "Office Space" and "Rock Star," not to mention "Along Came Polly" and "Bruce Almighty."
Her starring role, though, was in 2002's "The Good Girl," which won her acclaim. In it, she played a discount store clerk who strikes up an affair with a stock boy (Jake Gyllenhaal).
"'The Good Girl' was the first one where I felt like I was able to move away from what I had been known to do," she said.
Of course, Aniston is well-known for her 4 1/2-year marriage to Brad Pitt. They announced their separation in January and the divorce became final Oct. 2.
Since then, she has been rumored to be dating "Break Up" co-star Vince Vaughn.
But while Aniston's certainly gotten spicier in the pages of tabloid magazines lately, "Derailed" director Mikael Hafstrom said she uses her "sweetheart" image to her benefit even in this dark thriller.
"The general audience reaction to her is that she's trustworthy and, in this case, that's a good thing."
FOX News' Mike Waco and Trace Gallagher and the Associated Press contributed to this report.