Cussonia natalensis Sond. and C. zuluensis Strey have a long history of medicinal use in southern Africa. The aim of this study was to review the medicinal uses and pharmacological properties of the two species. Results of this study are based on data derived from several online databases such as Scopus, Google Scholar, PubMed and Science Direct, and pre-electronic sources such as scientific publications, books, dissertations, book chapters and journal articles. The bark, fruits and roots of C. natalensis and C. zuluensis are used as emetic, purgative and protective charm, and traditional medicine for diarrhoea, fever, stomach ache and swellings. This study showed that pentacyclic triterpene acids, cardiac glycosides, flavonoids, polyphenols, saponins and steroids have been identified from the leaves, roots and twigs of the species. The leaf extracts and compounds isolated from C. natalensis and C. zuluensis exhibited antibacterial, antifungal, antimalarial, antiprotozoal and cytotoxicity activities. Documentation of the medicinal uses, phytochemistry and pharmacological properties of C. natalensis and C. zuluensis is important as this information provides baseline data required for future research and development of health-promoting and pharmaceutical products. There is need for extensive phytochemical, pharmacological and toxicological studies of crude extracts of C. natalensis and C. zuluensis to establish the safety profiles of different preparations of the two species.