How you know her: The notoriously outspoken actress starred in My Father the Hero and Roswell and hit the big time as Izzie on Grey's Anatomy. She won an Emmy for Grey's in 2007, the same year she starred in Knocked Up, which led to one rom-com too many. She negotiated out of her Grey's contract in 2010.
The New Role: Heigl trades in her stethoscope for classified case files as CIA analyst Charleston Tucker (yes, that is her name), who advises the president (Alfre Woodard) and who was once engaged to POTUS' now-dead son. What's the hardest part of the show for her? "Mostly just trying to get people to believe I could be a CIA analyst," she quipped.