Polo has guest starred on many TV shows like The Practice, Felicity, Chicago Hope, Sports Night, Numb3rs, and Frasier. Polo's primetime debut was in "TV 101". She also stared in The Phantom of the Opera (1990 miniseries) as Christine Daae. She became a regular cast member on the last season of Northern Exposure, and the sixth and seventh seasons of The West Wing playing the role of Helen Santos, the wife of Democratic presidential candidate Matt Santos (Jimmy Smits). She has also hosted several ceremonies. Recently, she appeared on Fox's The Wedding Bells, portraying the wedding planner Jane Bell.

In February 2005, Polo appeared on the cover of, and posed nude in Playboy. The appearance was linked to the release of Meet the Fockers, with cover text that made similar plays on words such as “She's one hot Focker”. She was ranked #42 on the Maxim Hot 100 Women of 2002. She was also featured in InStyle.