The 35 previously described species (including 4 junior synonyms) of the New World erythroneurine leafhopper genus Zyginama are reviewed and descriptions are provided for 43 new species, 2 from U.S.A., 26 from Mexico, 1 from Panama, and 14 from the Amazon region of South America. The following new synonyms are recognized: Z. aucta (McAtee) equals Erythroneura bilocularis Van Duzee, syn. n., and E. inclita Beamer, syn. n.; Z. nicholi (Beamer) equals E. canyonensis Beamer, syn. n., and E. ales Beamer, syn. n. Separate keys are provided for identification of males from North and South America, all known species are illustrated, and data on their distributions are summarized. Phylogenetic analysis of 40 morphological characters of the 71 species for which males are known yielded a reasonably well resolved estimate of relationships among the included species, but branch support was low overall.