Species of the North American freshwater mussel (Unionidae) genus Villosa are reviewed. True Villosa are limited to the extreme southeastern United States. Additional nominal Villosa taxa are placed in the new genera Paetulunio (type species Unio fabalis), Cambarunio (type species Unio iris), Leaunio (type species Unio lienosus), and Sagittunio (type species Unio nasutus). Other species are allocated to the existing genera Obovaria and Venustaconcha. New taxa: Paetulunio n. gen., Cambarunio n. gen., Cambarunio dactylus anatinensis n. ssp., Cambarunio dactylus viridensis n. ssp., Cambarunio hesperus n. sp., Leaunio n. gen., Leaunio lienosus aquilonius n. ssp., Leaunio lienosus ouachitaensis n. ssp., Leaunio pataecus n. sp., Sagittunio n. gen., Sagittunio aldermani n. sp.