There is a continuous search for new medication against many diseases. The main reason is that existing remedies have unwanted side-effects and that they may lose their efficacy with time. Traditional medicinal plants are seen as an important source of possible new and interesting therapeutic drugs. Many of these plants, or preparations thereof, have shown their efficacy over the years but they have not been screened for potential adverse health effects as is the practice for modern medicines. It is therefore important to test such plants or their extracts for potential effects on health. We therefore investigated the genotoxicity of a number of Hypoxis species. This is important as preparations from them were highly promoted in the popular press in South Africa as agents that can also boost immunity in HIV/AIDS patients. Yet, there are unconfirmed reports of toxic properties and hence warnings against the use of Hypoxis and their products.We performed an in vitro evaluation of the genotoxic potential of water extracts from the Hypoxis species Hypoxis hemerocallidea, H. colchicifolia, H. rigidula and H. acuminata and from a commercial preparation thereof using the neutral red uptake (NRU) assay, the alkaline comet assay and the cytome assay in human hepatoma HepG2 cells. The relative cytotoxicity of these samples was established by determining their NI50 values (50% inhibition of NRU), and these results were used for dose-finding in genotoxicity tests. None of the tested extracts were identified as genotoxic in both the alkaline comet assay and cytome assay.