A checklist with preliminary conservation assessments of native South American species of Acalypha is presented. This work is supported by the study of ca 6500 herbarium specimens and an in-depth literature review. As a result, 87 species (83 native and four introduced) and eight subspecies are accepted, and a further 395 names are considered synonyms. Geographical distribution, habitat, and altitudinal range for all species are also indicated. Brazil is the richest country in number of species of Acalypha (40), followed by Peru (32), Bolivia (29), Colombia and Ecuador—including Galapagos Islands—(24), Venezuela (18), Argentina (17), Paraguay (13), Guyana (8), Uruguay (5), French Guiana (4), and Suriname (3). The presence of the genus Acalypha in Chile is reported for the first time, alongside new country records of A. poiretii in Peru and A. venezuelica in Guatemala. The specimens previously identified as A. plicata from Colombia and Venezuela, are here considered belonging to A. cuspidata. The red list provided follows IUCN criteria and includes 39 species and three subspecies, 47% of total native species of Acalypha in South America: 16 species and one subspecies Critically Endangered (nine of them probably extinct), 15 species and two subspecies Endangered, and eight species Vulnerable.