Private school-educated Bell was born to Jewish real estate developer Havey Siegel and his Protestant design firm owner wife, Robin Bell, in New York City. She was raised in nearby Connecticut and in Vero Beach, Florida. She attended Skidmore College in New York before she transferred to Rose Bruford College in London, where she appeared in drama school productions including The Seagull and Six Degrees of Separation.
Her career in Hollywood began in 2002, when she was cast in two episodes of ER and the feature film Speakeasy, which was the runner-up in the first season of reality series Project Greenlight, which offered a production prize to aspiring filmmakers. In 2003 she co-starred as Alicia Silverstone's wisecracking best friend in the short-lived TV series Miss Match, and the psychological thriller film I Love Your Work.
Her work on critically and commercially-acclaimed The Practice and its spinoff Boston Legal, soon followed, as did roles as Cameron Diaz' best friend in rom-com What Happens in Vegas, a starring role in Rampage: The Hillside Strangler Murders, a '70s set biopic about a notorious serial killer, and a role as Colin Farrell's wife in the crime drama Pride and Glory. The couple dated following filming, but had broken up by August 2006.
Since 2008, Bell has co-starred with Rob Corddry as Dr. Cat Black, in the satirical medical comedy Children's Hospital. She directed two episodes of season four of the series, and in 2013 released her feature directorial debut In A World... at the Sundance Film Festival. Bell has also modelled extensively, appearing everywhere from the catwalks at Milan Fashion Week to the pages of Maxim's Hot 100. She loves cars, and is the contributing automotive editor at The Hollywood Reporter magazine.
From 2010 to 2012, she co-starred on the HBO original series How to Make It in America. Artist Scott Campbell appeared as himself in an episode of season two, where he and Bell met and fell in love. They were married in New Orleans in June 2013, with their dogs, Texas and Margaret, serving as ring bearers and "dogs of honor."