Concerns regarding the conservation of medicinal plant species are receiving much attention due to overharvesting and exploitation. Medicinal plant harvesting is a global concern as plants are the source of the majority of medicines, either traditional or western, in the world. Millions of U.S. dollars of plant material are being exported annually from developing countries to developed countries. The challenge in developing countries is that, apart from the exports, the majority of people in those countries still use medicinal plant material for their basic healthcare needs. Biodiversity loss is therefore a significant challenge. This review focuses on South Africa as a developing country in which traditional medicines are highly valued, but also engages in exports of medicinal plant material to developed countries. Medicinal plant harvesting, with reference to suppliers of medicinal plant material, customary knowledge and the drivers of increased harvesting rates in South Africa is discussed. General aspects of sustainability and the causes of unsustainable medicinal plant harvesting, as well as cultivation to increase medicinal plant populations referring to its advantages and disadvantages and the challenges regarding cultivation of medicinal plant species for the medicinal plant trade market are reviewed. The shift from a cultural method of survival to a competitive trade business, South Africa's legislation regulating the management of natural environments, legislation compliance and the regulation of African traditional medicine are also reviewed. •Commercial harvesters use environmentally destructive harvesting methods.•Legislation failed to prevent illegal harvesting and trade in South African indigenous plants.•There is a relationship between resource stock, population size and sustainable harvesting rates.•Information on how much plant material constitutes sustainable harvesting is totally lacking.•Cultivation provides advantages over wild stocks for the production of plant based medicines.