Blair was in a relationship with her childhood sweetheart who died in 1990, at the age of 18. In July 2003, she began her love affairs with Ahmet Zappa. Ahmet is a famous writer, producer, and publisher from the United States and after dating each other for about six months, they got married on 24 January 2004. On June 21, 2006, Blair filed for divorce from her husband of two years citing "irreconcilable differences." Their divorce was finalized in December 2006.
Blair was in a relationship with her Kath and Kim co-star Mikey Day from 2008-2010. Blair dated fashion designer Jason Bleick, with whom she shares a child, for two years. Thier child, a son named Arthur Saint Bleick was born on July 25, 2011.
Blair attended Hillel Day School, a Jewish day school in Farmington Hills and Cranbrook Kingswood in Bloomfield Hills both in Michigan. Blair was interested in drama and arts was since her childhood days. While she was at New York Universtiy, she also took several acting classes. She is the graduate of the University of Michigan and has a BFA degree in Photography.
Blair became active in the entertainment industry since 1995 and her role in the TV show The Adventures of Pete & Pete was her debut acting role. The following year she made her big-screen debut, appearing in The Broccoli Theory.
In 2004, she was cast as Jane Burns alongside Cameron Diaz, who played Christina Walters in The Sweetest Thing. In 2005, she had her major commercial success, The Fog. The thriller/action movie made a gross collection of $46.2 million.
In 2006, Blair was cast a voice artist for Hellboy: Swords of Storms and Hellboy: Blood and Iron. In 2008, she cast in the sequel of Hellboy, Hellboy II: The Golden Army as Liz Sherman. Made on a budget of $85 million the movie made a gross collection of $160.4 million. In 2017, she appeared in Brian Taylor's directorial Mom and Dad. She was cast alongside actor Nicolas Cage in Mom and Dad.
Blair's major TV shows are Xena: Warrior Princess (2000), Frineds (2002), Anger Management (2012-2013) and American Crime Story (2016).
Till now, Blair has appeared in more than fifty movies and television series. She has amassed a fortunate income form her acting career. Her current net worth is estimated at $14 million and has an annual income in the neighborhood of $1.6 million. For her role in Anger Management, she earned the salary of $40,000 for each episode and her net worth is rumored to be in millions.
In 2012, Blair listed her Los Angeles mansion up for sale, with asking price of $1.78 million.