Gilsig began acting at age twelve while living in Montreal. She later honed her talents at Harvard University’s prestigious American Repertory Theatre. In 1995 she moved to New York City where she appearing in several off-Broadway plays. Although she had appeared in several Canadian productions in the late 1980s/early 1990s, her television career began during the late 1990s when she guest-starred in several television series, including Viper and Seven Days. However, it was her association with David E. Kelley that led to her starring role in Boston Public.

After guest-starring in two episodes of Kelley's The Practice, Gilsig was cast in two episodes of another Kelley program, the short-lived Snoops. Although the series was cancelled before Gilsig's episodes were broadcast, Kelley wrote the part of Lauren Davis in Boston Public specifically for her. The series premiered in September of 2000 on FOX. Gilsig left the series after the end of the season in May 2002. The reason for her leaving Boston Public after was never officially revealed.

Following her departure from Boston Public, Gilsig joined the cast of Nip/Tuck in 2003, a role she continues to this day. In 2004 she appeared in five episodes of NYPD Blue, followed by four episodes of FOX's Prison Break in 2005. In early 2006 she guest-starred in an episode of Law & Order.

In addition to her extensive credits in television and theatre, Gilsig also has some experience with the big screen. She had a small role in the 1998 film The Horse Whisperer and provided the speaking voice for Kayley in the animated Quest for Camelot (Andrea Corr performed the character's songs), also released in 1998. In 2004 she appeared in Chicks with Sticks as well as See This Movie.