Kihlstedt was born in Lancaster, Pennsylvania and is a 1991 graduate of Skidmore College in Theatre Arts. She is of Nicaraguan descent.[citation needed]
Kihlstedt made her film debut starring opposite Rutger Hauer in the 1993 action thriller film Arctic Blue. In 1995, she appeared in the ABC miniseries Heaven & Hell: North & South, Book III and in 1995 played Lizzie Elmsworth in the BBC adaptation of Edith Wharton's last novel, The Buccaneers. In 1997, she starred as Alice Ribbons, one of the criminals in the family comedy film Home Alone 3. The following year, she appeared in the science-fiction film Deep Impact, and co-starred opposite Carla Gugino in the independent film Jaded. Also in 1998, Kihlstedt starred with Peter Gallagher in the television film Brave New World loosely based on Aldous Huxley's 1932 novel of the same name.
Kihlstedt took a ten-year break from acting as she focused on motherhood and raising her two children. In 2009, she returned to screen appearing opposite her friend Carla Gugino in the comedy film Women in Trouble, and its sequel, Elektra Luxx. She guest-starred in a number of television series, including Covert Affairs, Criminal Minds, NCIS, CSI: Crime Scene Investigation, and Drop Dead Diva. In 2011, she had a recurring role in the Showtime crime drama series Dexter as Dr. Michelle Ross. From 2012 to 2013, she played Marilyn Rhodes, a powerful record producer in the ABC musical drama Nashville. Also in 2013, she starred in the comedy film 3 Days in Havana directed by her husband Gil Bellows.

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