The 21st Independent Spirit Awards, honoring the best in independent filmmaking for 2005, were announced on March 4, 2006. It was hosted by Sarah Silverman.

The Squid and the Whale is a 2005 American independent comedy-drama film written and directed by Noah Baumbach and produced by Wes Anderson. It tells the semi-autobiographical story of two boys in Brooklyn dealing with their parents' divorce in 1986. The film is named after the giant squid and sperm whale diorama housed at the American Museum of Natural History, which is seen in the film. The film was shot on Super 16 mm, mostly using a handheld camera.