Sandsage prairie is a shrub-steppe ecological system of the Great Plains of North America in which sand sagebrush (Artemisia filifolia) is dominant and diagnostic. An estimated 5 million hectares of sandsage prairie occurs in discontinuous tracts across eight states in association with dune fields and other sandy habitat. This paper documents the biodiversity attributes of sandsage prairie, which is an ecological system of conservation concern due to range-wide declines in areal extent and ecological integrity. Sandsage prairie hosts many regional endemics, ecological specialists, and species of conservation concern at the state and global levels. It is particularly important to avian ecology in the Great Plains, with 14 species of endemic or obligate grassland birds utilizing sandsage prairie for breeding and/or foraging habitat. In many parts of its range, sandsage prairie is the only native vegetation of significant scale remaining on the landscape, providing islands of natural habitat critical to the support and persistence of biological diversity. These attributes make sandsage prairie a biodiversity hotspot for the central and southern Great Plains. Stewardship of sandsage prairie biodiversity requires preventing further loss, fragmentation, and degradation of existing occurrences as well as accommodating or restoring processes that drive the inherent heterogeneity of this unique ecological system.