We compared the fauna of small mammals (less than 500 g body weight) among five major South American drylands (Atacama, Altiplano, Monte, Patagonia and Caatinga) and found considerable heterogeneity and distinctiveness in species richness and composition between these biomes. From a total of 89 recorded species, 76 of them are restricted to only one of these drylands. The highland desert, or Altiplano, is the biome with the highest number of species. Despite the marked differences in the composition of the mammalian fauna, the trophic structure shows a rather consistent pattern: herbivores are the most important trophic group in all drylands. This consistency seems to be more the result of phylogenetic inertia than of similar ecological processes. Our results are compared with recent studies on desert small mammals across continents.