The revision of Metastelma (Apocynaceae–Asclepiadoideae) in southwestern North America and Central America (excluding the Caribbean) is based on field observations and study of herbarium specimens. Sixteen species are recognized (two of these split into two subspecific units, two into three subspecific units). Two new taxa, M. barbigerum var. veracruzense and M. schlechtendalii var. arenicola, are described. Two former species are reduced to subspecific rank (M. arizonicum subsp. chiapense and M. californicum subsp. lanceolatum) and two to varietal rank (M. barbigerum var. liesneriana and M. schlechtendalii var. trichophyllum). One taxon (M. turneri) is raised from varietal to species rank. Four new synonyms are recognized: Ditassa mexicana as synonym to M. californicum subsp. lanceolatum, M.infimicola as synonym to M. eliasianum, M. macropodum as synonym to M. palmeri, and M. multiflorum as synonym to M. schaffneri. The morphology of the North and Central American species of Metastelma, as well as habitats, distribution, and phenology, are described. In addition to the taxonomic descriptions, illustrations and distribution maps are presented for each species.