She was born on November 30, 1971 in Montreal, Quebec, Canada, the daughter of Claire, a writer and translator, and Toby Gilsig, an engineer. She began her acting in a voice work part at age 12 for a National Film Board of Canada production, Masquerade.
Gilsig attended McGill University in Montreal, from 1989 to 1993, graduating with a Bachelor of Arts degree in English in 1993. She later pursued her acting studies further at Harvard University's Institute for Advanced Theater Training.
Gilsig began her career as a voice actress. She has done voices in the films such as Masquerade, and for television series such as Young Robin Hood.
She moved to New York City in 1995 where she appeared in several off-Broadway plays. 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, a series that premiered in September 2000 on FOX; Gilsig would leave the series after the end of the second season in May 2002.
Following her departure from Boston Public, Gilsig joined the cast of Nip/Tuck in 2003 as Gina Russo, a role she continued until 2008. In 2004, she appeared in five episodes of NYPD Blue, followed by four episodes of FOX's Prison Break in 2005.
In addition to her extensive credits in television and theatre, Gilsig has appeared in film, beginning with a small role in the 1998 film The Horse Whisperer. She then provided the speaking voice for Kayley in the animated film Quest for Camelot (1998), with Andrea Corr performing the character's songs. In 2004 she appeared in Chicks with Sticks, as well as See This Movie, and in one of the lead roles in the 2007 movie, Flood.
In 2007-2008 she had recurring roles in two television series, playing Shelley, the sister of Tami Taylor, on NBC's Friday Night Lights, and Claire Bennet's biological mother, Meredith Gordon, on Heroes. Gilsig went on to play the main role of Terri Schuester on the Fox show, Glee, from 2009-2012.
In 2013, Gilsig was a series regular, portraying Siggy Haraldson, wife of Earl Haraldson and paramour of Ragnar Lothbrok's brother, Rollo, on the History Channel series Vikings until 2015. In 2017 she will be joining the cast of Scandal.
Gilsig met and briefly dated her future husband Bobby Salomon as a high school student - he was the football team quarterback she described as a "cool guy"; after Salomon, a film producer, moved to Hollywood in 2002, he and Gilsig renewed their friendship, began dating again, and married on January 1, 2005 in a traditional Jewish wedding (Gilsig being Jewish on her father's side). Gilsig and Salomon have a daughter, Penelope, born on September 26, 2006.
Gilsig filed for divorce from Salomon on September 8, 2010, citing irreconcilable differences, having been separated since 2009. In 2013 Gilsig became an American citizen.