We present a taxonomic revision of Serpocaulon A. R. Sm. (Polypodiaceae), a tropical American fern genus. Our work is based on a morphological analysis of 56 characters recorded from 2167 specimens deposited in 41 herbaria. Field trips were carried out in Argentina, Bolivia, Brazil, Colombia, Costa Rica, Ecuador, Panama, and Peru, where observations on the habit and habitat of several species were made. Digital images were also consulted. A total of 260 names were found and their nomenclatural types were studied, resulting in the lectotypification of 47 names (first-step 30, second-step 17 names). We recognize 37 species and five hybrids in Serpocaulon; one of the hybrids is given a new status (S. ×semipinnatifidum (Fée) A. R. Sm.) and another one is described (S. ×tabuleirense D. Sanín & Salino). Moreover, 19 names are newly synonymized, five species are excluded, 17 names are considered as of uncertain application, and five as nomina nuda. We document for 22 species a total of 62 chorological novelties in different countries. The elevational range of the genus is 0–4200 m. The Andes of Ecuador and Colombia are the main center of diversity and endemism; secondarily, the Atlantic Rain Forest of Brazil has five endemic species. We provide a taxonomic key, descriptions, discussions, local names, uses, illustrations, photographs of the plants in the field, microphotographs of the rhizome scales and the spores, and distribution maps of all species.