Malaria is endemic to many countries of northern South America. There is a rich traditional use of plants to treat malaria in this region. This review focuses on species from the Gentianaceae that are used in South America to treat malaria, fevers, and symptoms related to malaria. Species names used in original works are revised in accordance with contemporary knowledge of botany and distribution of these plants. Gentians from the following neotropical genera are used as antimalarials, those being Calolisianthus Gilg, Centaurium Hill, Chelonanthus Gilg, Coutoubea Aubl., Curtia Cham. and Schltdl., Deianira Cham. and Schltdl. Eustoma Salisb., Gentiana L., Gentianella Moench, Schultesia Mart., Tachia Aubl., and Voyria Aubl. Several gentian extracts and substances exhibit in vitro and especially in vivo antimalarial activity based on pharmacological and chemical composition studies. Water–ethyl alcohol extracts of the bark and roots of Potalia resinifera Mart., chloroform fractions of the ethyl alcohol extracts of leaves, and the methyl alcohol extracts of roots of Tachia grandiflora Maguire and Weaver inhibited Plasmodium falciparum (a human malaria parasite) in vitro. In vivo antimalarial activity in rodent models has been reported for ethnopharmacologically relevant extracts of Calolisianthus speciosus Gilg, Chelonanthus Gilg sp., and Tachia Aubl. spp. [originally cited species: Irlbachia speciosa (Cham. and Schltdl.) Maas, I. alata (Aubl.) Maas, Tachia guianensis Aubl., respectively], and T. grandiflora. The pharmacological potential has been explored of only a few gentians from South America. Active antimalarial gentians need further study to identify their active principles and to confirm scientifically their medicinal potential.