Three genera are separated here from the South American Capparis s.l. (Capparaceae): (1) Sarcotoxicum, a new monospecific genus restricted to Bolivia, Paraguay, and northern Argentina, composed of Sarcotoxicum salicifolium comb. nov.; (2) Neocalyptrocalyx is validated as a genus of seven species, with the following five species herewith transferred from Capparis s.l.: Neocalyptrocalyx eichleriana comb. nov., N. grandipetala comb. nov., N. leprieurii comb. nov., N. maroniensis comb. nov., and N. muco comb. nov.; and a sixth species, N. longifolium comb. nov., is transferred from Colicodendron; and, (3) Mesocapparis stat. nov., a scandent- shrubby monospecific genus endemic to Brazil, comprised of the new combination Mesocapparis lineata comb. nov. They are characterized by a variously stellate pubescence, 2-seriate sepals, 7 to 37 stamens, and pepos or amphisarca bearing many seeds with white- to cream-colored embryos and convolute cotyledons. Illustrations, descriptions, and a key to the discussed genera are herewith provided.