In 2002, Wettig was a regular cast member in the short-lived Bravo drama series "Breaking News". From 2002 to 2004, she played the recurring role of CIA psychotherapist Dr. Judy Barnett on "Alias" (on which her husband was a producer and director). From 2005 to 2007, Wettig appeared in 18 episodes of Fox television drama, "Prison Break", playing fictional Vice President Caroline Reynolds. She turned down Fox's offer of becoming a series regular on "Prison Break" in order to pursue the ABC comedy-drama series "Brothers & Sisters", which debuted in September 2006. Wettig starred in the series as the Walker family patriarch's mistress, Holly Harper. She left the show midway through the show's fifth and final season after her character "Holly Harper" followed her daughter to New York along with her fiancé David played by real life husband Ken Olin.