Virginia Madsen was born on September 11, 1961, in Chicago, Illinois, to Elaine Madsen, an Emmy Award-winning filmmaker and author, and Calvin Madsen, a firefighter. Her brother, Michael Madsen, is also an actor, known for his roles in films like "Reservoir Dogs" and "Kill Bill."

Virginia Madsen attended New Trier High School in Winnetka, Illinois, and later studied at the Ted Liss Acting Studio in Chicago and the Harand Camp Adult Theater Seminar in Wisconsin.

She made her film debut in 1983 with a small role in "Class," but her breakout performance came the following year when she played Princess Irulan in David Lynch's "Dune." She gained mainstream popularity with her role in "Fire with Fire" (1986) and received critical acclaim for her performance in "Candyman" (1992), for which she won a Saturn Award for Best Actress.

In 2004, Virginia Madsen was nominated for an Academy Award for Best Supporting Actress for her role as Maya Randall in "Sideways."

Other notable films in her career include "The Prophecy" (1995), "Ghosts of Mississippi" (1996), "The Rainmaker" (1997), "A Prairie Home Companion" (2006), "The Number 23" (2007), "The Haunting in Connecticut" (2009), "Joy" (2015), and "Lola" (2024).

She has also had a successful career on television, with recurring roles on shows like "Moonlighting" (1989), "Frasier" (1998), "American Dreams" (2002-2003), "Monk" (2009), "The Event" (2011), "Hell on Wheels" (2012), "Witches of East End" (2013-2014), and "Designated Survivor" (2016-2017).

Virginia Madsen has been married twice. Her first marriage was to actor and director Danny Huston in 1989, and they divorced in 1992. She later married Nick Holmes in 2020. She has one son, Jack Sabato, born in 1994.