The southeastern United States contains ca. 250 species of crayfish. Of these, 85 are historically known from Alabama. Previous studies have shown that the Sipsey River drainage in western Alabama is a diversity “hotspot” for freshwater mussels (42 spp.) and fishes (102 spp.). This is attributed to diverse geologic features, an intact floodplain, lack of impoundments, and lack of urban centers. Intensive sampling of the Sipsey River drainage over a 2-year period resulted in a collection of 294 crayfish representing 12 species. Three of these species, Cambarus ludovicianus, Orconectes chickasawae, and Procambarus vioscai paynei are of conservation concern. Our results indicate that the Sipsey River harbors a greater richness of crayfish species per area than other drainages surveyed to date in Alabama.