We present a revised list of freshwater mussels (order Unionida, families Margaritiferidae and Unionidae) of the United States and Canada, incorporating changes in nomenclature and systematic taxonomy since publication of the most recent checklist in 1998. We recognize a total of 298 species in 55 genera in the families Margaritiferidae (one genus, five species) and Unionidae (54 genera, 293 species). We propose one change in the Margaritiferidae: the placement of the formerly monotypic genus Cumberlandia in the synonymy of Margaritifera. In the Unionidae, we recognize three new genera, elevate four genera from synonymy, and place three previously recognized genera in synonymy. We recognize for the first time two species (one native and one nonindigenous) in the Asian genus Sinanodonta as occurring in North America. We recognize four new species and one subspecies and elevate 21 species from synonymy. We elevate 10 subspecies to species status and no longer recognize four subspecies. We change common names for five taxa, correct spelling for eight species, and correct the date of publication of original descriptions for four species.