This article examines in detail the ingenious ways in which Sherman Alexie appropriates the blues as a vessel for Native Americans to creatively express their predicament and a subversive instrument in their struggle to resist colonial cooption. In Reservation Blues (1995) Alexie’s writing itself creates a Native American version of the blues that appropriates such blues staples as the AAB stanza, improvisation, and syncopation. The author’s multiple references in the novel to mainstream popular culture are in contrast to the role of the blues, which arguably serves as the music of choice for Alexie’s principal project: the survival of Native America.