She's perhaps best known for her role as Janis Ian in cult film Mean Girls, but she's also highly versatile with many appearances in film and television. She starred on the critically acclaimed Masters of Sex as Virginia Johnson, for which she gained notable press.
- 2004 Mean Girls as Janis Ian
- 2008 Cloverfield as Marlena Diamond
- 2008 My Best Friend's Girl as Ami
- 2010 Hot Tub Time Machine as April Drennan
- 2010 127 Hours as Sonja Ralston
- 2012 Bachelorette as Gena
- 2012 Item 47 as Clare
- 2014 The Interview as Agent Lacy
- 2016 Now You See Me 2 as Lula May
- 2018 Extinction (2018) as Alice
- 19992000 Freaks and Geeks as Sara
- 2001, 2003 Smallville as Tina Greer
- 2003 The Pitts as Faith Pitt
- 2005 Tru Calling as Avery Bishop
- 20062009 American Dad! as Debbie
- 20062007 The Class (2006) as Kat Warbler
- 2008 True Blood as Amy Burley
- 20092010 Party Down as Casey Klein
- 2012 New Girl as Julia
- 20132016 Masters of Sex as Virginia Johnson
- 2018 Das Boot
- 2019 Castle Rock as Annie Wilkes
- 2021 Inside Job as Reagan Ridley
- Ability over Appearance: The Mean Girls producers thought Lizzy Caplan was too pretty for "art freak" Janis, but eventually cast her due to considering her the best actress that auditioned.
- Brainy Brunette: In most of her roles.
- Contralto of Danger: She has a surprisingly deep voice, especially for her younger roles.
- Deadpan Snarker: Watch any interview with her. It's little wonder she often plays snarky Ensemble Dark Horse types.
- Ms. Fanservice: In both Masters of Sex and True Blood.