Wettig starred in the ABC comedy-drama series Brothers & Sisters, which debuted in September 2006, where she portrays the Walker family patriarch's mistress, Holly Harper. Her character was the co-CEO at Ojai Foods with Sarah Walker, the daughter of William Walker. She left the show mid-season during Season 5 after her character Holly Harper followed her daughter to New York along with her fiance David played by real life husband Ken Olin. This season sees the whole Harper family absent from the show. Wettig also had the recurring role of CIApsychotherapist Dr. Judy Barnett on Alias (husband Olin was a producer and director on the series). Before joining Brothers & Sisters, she played the fictional Vice PresidentCaroline Reynolds on the 2005 Fox television drama, Prison Break. She turned down Fox's offer of becoming a series regular on Prison Break in order to pursue Brothers & Sisters. In 2007 ABC and FOX agreed that Wettig could briefly reprise her role as Caroline Reynolds, providing off-camera voice-overs and appearing in a scene with Wentworth Miller.
Patricia Wettig and Ken Olin on the red carpet at the 41st Annual Emmy Awards
Wettig is married to actor and producer Ken Olin; they have two children, Clifford (b. 1983) and Roxanne (b. 1985). Their daughter, Roxanne (better known as "Roxy"), was a principal cast member of the MTV series The City, and also had a regular role on the ABC Drama Brothers & Sisters.