Three seasons into Buffy the Vampire Slayer, Sarah Michelle Gellar let loose in 1999's cult classic Cruel Intentions, playing a prep school mean girl who's as poisonous as the monsters Buffy fights at night.
Gellar wasn't the only Cruel Intentions cast member breaking out of a TV mold. Jackson, who was one season into his role as jokester-turned-love interest Pacey Witter on Dawson's Creek, bleached his hair and embraced sweater vests as Blaine, gay best friend to Ryan Phillippe's Sebastian.
It's hard to remember a time when charming rom-coms weren't a cornerstone of Jennifer Garner's brand. But in 2004, 13 Going on 30 was a departure for the actress, who was three seasons deep in her breakout role as ass-kicking spy Sydney Bristow on Alias. Garner even commented to the press that it was "weird" to see herself "smile so much" on the big screen.
A year after Steve Carell became a household name pushing papers as Michael Scott on The Office, he went to a darker place for indie hit Little Miss Sunshine. As Frank, a depressed Proust scholar recovering from a recent suicide attempt, Carell distanced himself from his bumbling sitcom character by playing the most serious person in the room.
In 2011, Jon Hamm was four seasons into his career-making turn as Mad Men's slick ad executive Don Draper -- but his delightfully silly performance as an alpha-male jerk in Bridesmaids showed audiences that the actor could really land a joke.
Aniston's performance as a lonely, unhappily married woman in 2002's The Good Girl had critics raving. The role was a far cry from the plucky, privileged Rachel Green on Friends, which was entering its ninth season at the time.
Three years after Mary Tyler Moore's eponymous series went off the air, the actress proved herself capable of playing more than spunky sitcom characters. Her complex performance as an unsympathetic mother in Ordinary People landed her an Oscar nomination.
Gillian Anderson, then seven seasons deep in her career-defining role as The X-Files' skeptical FBI agent Dana Scully, traded pantsuits for parasols to play New York socialite Lily Bart in a 2000 adaptation of Edith Wharton's The House of Mirth.
Lively was still playing a high-fashion, high-society teen on Gossip Girl when she nabbed the role of a 29-year-old, drug-dealing single mom from Boston in Ben Affleck's The Town.
After six seasons as dim-witted goofball Kelso on That '70s Show, Kutcher went dramatic in psychological thriller The Butterfly Effect, playing a college student who could travel into his own past.
Two seasons into her breakout role as romance writer Jane Villanueva on Jane the Virgin, Rodriguez got her hands dirty as a tough oil rig operator in Deepwater Horizon.
After stepping down from her throne as The Crown's Queen Elizabeth II, Foy went as far away from Buckingham Palace as she could get when she took on the role of edgy computer hacker Lisbeth Salander in The Girl in the Spider's Web.
Just a month after the final episode of The Fresh Prince of Bel-Air, Will Smith cemented his status as a Hollywood leading man -- and action star -- as the charismatic Captain Steven Hiller in Independence Day.
When Dawson's Creek ended in 2003, Holmes set out to prove she was more than "girl next door" Joey Potter by playing a struggling young woman trying to make it in New York City in Pieces of April.
Five seasons into her role as Rory Gilmore, the ultimate high achiever, on Gilmore Girls, Bledel took a detour from Stars Hollow when she played a young prostitute in 2005 neo-noir film Sin City.