From the mid-1990s (while at Northwestern University) through 2001, Dudek appeared in various theater productions and on Broadway. She made her Broadway debut in Wrong Mountain in 2000, and won the Connecticut Critics Circle Award for outstanding performance in The Glass Menagerie.

Dudek had a recurring role on House as Amber Volakis (scorned by Dr. House as "Cutthroat Bitch"), one of ten physicians under consideration by Dr. House for permanent positions on his team. Her character survived the first series of cuts but was eliminated in the ninth episode of season 4. She then returned briefly as the love interest of Dr. Wilson, but her character died after sustaining fatal injuries in a bus crash in the season 4 finale "Wilson's Heart". Most recently, she has appeared in Mad Men as next-door neighbor Francine Hanson, and on Big Love as one of antagonist Alby Grant's wives, both recurring roles.

On film, she played the role of cruise line heiress Tiffany Wilson in the 2004 comedy film White Chicks. She also played Anthony Hopkins' daughter in The Human Stain.

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