Ethnopharmacological relevance: Hypoxis species (Hypoxidaceae) are popular medicinal plants used in the African traditional medicine to treat numerous ailments and are reported to have a wide spectrum of pharmacological properties. In this paper we reviewed and evaluated the traditional uses, pharmacological, phytochemistry and toxicity aspects of the genus Hypoxis. Potential medicinal prospects and possible knowledge gaps and pitfalls are discussed. Materials and methods: A comprehensive and systematic review of literature on Hypoxis species was done using numerous resources such as books and scientific databases that include Pubmed, Scopus, Scirus, Google scholar, Web of Science and others. Information on the various pharmacological and chemical properties of Hypoxis extracts was critically analysed and discussed under the various topics. Results: The literature indicated a broad range of uses, pharmacological and toxicological properties of different Hypoxis species extracts and their relevance to African healthcare systems. Several compounds, mostly glucosides, sterols and sterolins, have been isolated, identified and tested in various in vitro and in vivo models as well as in a couple of clinical trials with a lot of promising prospects reported in some studies. Conclusion: A critical analysis of the available literature and studies identifies positive potential for the future use of Hypoxis species in both traditional and modem medicine and concurrently so with possible pitfalls and research gaps in current knowledge. An integrated and holistic approach to addressing research issues, particularly toxicology aspects could be more effectively applied and incorporate conservation strategies for the species. (C) 2013 Elsevier Ireland Ltd. All rights reserved.