Based on the long history of medicinal plant use, users of traditional medicines accept that they are safe for human consumption. However, the absence of regulation of the medicinal plant trade in aspects such as collection, processing and storage provides no such guarantee. Environmental pollution, misidentification and adulteration provides further grounds for concern. The potential adverse effects of South African traditional medicines are not well documented. There are only a few investigations of mutagenic properties and heavy metal contamination. In the absence of regulatory controls, the safety and quality of medicinal plants vary considerably. The current comprehension and future challenges regarding quality, safety and efficacy of South African traditional medicine are discussed.