She is best known for her roles as Meredith Gordon in Heroes, Kayley in Quest for Camelot, Lauren Davis in Boston Public, Gina Russo in Nip/Tuck, Terri Schuester in Glee, and as Siggy Haraldson in Vikings.

[2] She began her acting in a voice work part at age 12 for a National Film Board of Canada production, Masquerade.

[8] She then provided the speaking voice for Kayley in the animated film Quest for Camelot (1998), with Andrea Corr performing the character's songs.

[15] In 2007–2008 she had recurring roles in two television series, playing Shelley, the sister of Tami Taylor, on NBC's Friday Night Lights,[16] and Claire Bennet's biological mother, Meredith Gordon, on Heroes.

[21] On January 24, 2020, Gilsig joined the cast of the Disney+ sports comedy-drama series Big Shot as Holly Barrett with John Stamos to replace Shiri Appleby.

[22] Gilsig met and briefly dated Bobby Salomon as a high school student – he was the football team quarterback she described as a "cool guy".