Citharexylum L. belongs to the recently circumscribed tribe Citharexyleae of the Verbenaceae, along with Rehdera Moldenke. It comprises around 50 to 60 species of trees and shrubs growing in the Neotropics. A complete taxonomic revision of Citharexylum in South America is here provided for the first time. Thirty taxa are present in South America, 27 of these are endemic, and three of them also grow in Central America. Detailed morphological descriptions are given for each taxon, as well as a key for their identification; illustrations, photographs, or iconography; updated synonymy; geographic distribution maps and ecological notes; list of selected specimens; and discussion about the relationship among closely related taxa. A new status, C. poeppigii Walp. var. anomalum (Moldenke) N. O'Leary, and a new combination, C. dentatum D. Don var. canescens (Moldenke) N. O'Leary, are proposed. Thirty-five new synonyms are suggested, and lectotypes are designated for C. fruticosum L. var. brittonii (Moldenke) I. E. Méndez, C. laurifolium Hayek, and Rauvolfia spinosa Cav.