She has appeared on a number of primetime television shows, starting with Foley Square, Leg Work, and several early episodes of Chicago Hope.

In 2003, she appeared in an episode of Law & Order: Special Victims Unit titled "Tortured", playing a mother/bakery owner who was later arrested for abetting a murder.

Colin has also been in a number of films, some of the most well-known including Something Wild (1986), Three Men and a Baby (1987), The Butcher's Wife (1991), Independence Day (1996), The Devil's Own (1997), Unfaithful (2002), and First Daughter (2004).

[5] In 2017, Colin appeared as a recurring character throughout the sixth season of the HBO comedy series Veep, playing fictional CBS News anchor Jane McCabe.

Along with her fellow cast members, Colin won the Screen Actors Guild Award for Outstanding Performance by an Ensemble in a Comedy Series.