Rising demand for medicinal plants has led to increased pressure on wild plant populations. This, combined with shrinking habitats, means that many species in South Africa are now facing local extinction. In 1997, a study was initiated to determine the extent of trade in medicinal plants in the South African Lowveld (the low lying plains to the east of the Drakensberg escarpment), and to investigate socio-economic factors influencing trade and resource management. Trade was not as extensive in the Lowveld as in major urban markets such as Durban or the Witwatersrand (Johannesburg and surrounding towns), either in terms of the quantity, number or range of species sold, or the numbers of people relying on the trade for an income. In markets assessed in Mpumalanga Province, 176 species were identified (71% of the vernacular names encountered in the market place), representing 69 plant families. In Limpopo, 70 different species were identified (84% of the vernacular names encountered in the market place), representing 40 families. Imports were significant in Mpumalanga (33% of the plants on offer), mainly from Mozambique. A detrended correspondence analysis showed substantial differences between species traded in Mpumalanga and those sold in Limpopo. There was little variation in the species stocked by vendors in Mpumalanga, regardless of the season, the attributes of the seller, or whether business was carried out in urban or rural areas. In contrast, there was considerable variation in the stock inventories of the Limpopo traders. Despite the lower levels of local trade, increased harvesting pressure is being experienced regionally, to meet demand in metropolitan centres such as the Witwatersrand. This study showed considerable local variation and complexities in the harvesting and marketing of medicinal plants, with both a national and an international dimension. This dual spatial scale presents both opportunities and challenges in the management of these plants, which need to be addressed simultaneously, particularly with respect to research requirements and development of predictive models and capacity. Cooperation in conservation strategies and policies is required at regional, national and international levels, while ensuring that management initiatives take into account local market conditions and the socio-economic realities facing both consumers and those who depend on the trade for their livelihoods.