Van Straten was born in Racine, Wisconsin, to Ralph and Sara Neubauer. Her father was an avid horseman and gun collector and her mother was a housewife involved in charities. In childhood she played sports and, like her father, rode horses and shot guns. She graduated from The Prairie School in Racine.
Van Straten studied fine arts at Washington University in St. Louis as well as in Boston and New York (Parsons The New School for Design) in her youth, but decided to become an actress and moved to Los Angeles, where she has been living since she began acting in 1994. She continues to draw and paint. Her works include commissioned portraits.
In 1995 she had her first recurring role in a television series, as Maggie Reynolds on The Crew. Other recurring roles are those of Geneva Renault in Total Security, Candy Cooper in That's Life, Rebecca Colfax in Dirty Sexy Money, and Belinda Slypich in Hidden Hills.
Perhaps her best-known film role was in Dancing at the Blue Iguana in 2000. Van Straten played a porn star appearing as the featured act at a Los Angeles strip club and performed an extended nude dance. In 2001 she starred in the award winning short film Room 302 and in 2004 she had a minor role in 50 First Dates, starring Adam Sandler. In the animated series Justice League she supplied the voice of the superhero Mera.
She has also made a number of guest appearances in several television shows, including LA Law, Seinfeld, Everybody Loves Raymond, Dark Angel, Two and a Half Men, Star Trek: Enterprise, CSI: Crime Scene Investigation, Desperate Housewives, and George Lopez.
She famously appeared in a Seinfeld episode ("The Bizarro Jerry") as Gillian, Jerry's girlfriend with "man hands". Van Straten currently stars as vampire Pam on the HBO series True Blood.
Van Straten has also been cast in the 2011 fantasy TV Series, Once Upon a Time, as the evil Maleficent, of Disney's Sleeping Beauty fame, the rival of the Wicked Queen of Snow White.
Van Straten carries out conservation work to improve the treatment of animals. She lives with many rescued animals at her home in Los Angeles.
On August 1, 2009, Van Straten married South African musician Abri van Straten, of the group The Lemmings, at her family’s farm in Wisconsin.
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