Taxonomic treatments of Pilosocereus in the Andean and Caribbean regions have varied widely. Recent authors often recognized three species only (P. lanuginosus, P. polygonus, and P. royenii), while Britton & Rose in 1920 (sub Cephalocereus) recognized 18 species in the same region. A revision of Pilosocereus is necessary, and it was carried out by the study of both herbarium specimens and living plants. Twelve species of Pilosocereus are recognized in the present paper for the Andean and Caribbean regions, including one new combination, i.e. P. curtisii, and one new species, i.e. P. jamaicensis. Typifications are provided for several names, including the Linnaean basionym Cactus royenii. Morphological descriptions, distributions, and an identification key of the recognized species are provided.