The Vhembe Biosphere Reserve (VBR) was inscribed on the United Nations Educational, Scientific and Cultural Organisation World Network of Biosphere Reserves in 2009, becoming the sixth South African biosphere reserve and the third in Limpopo Province. The unique biological and heritage features of the Soutpansberg (a recognised centre of floristic diversity and endemism) and Limpopo Valley, together with its largely rural population with high, direct reliance on natural resources, lend the area to a sustainable development model which integrates conservation, development and logistical support as stipulated in the Man and the Biosphere programme. However, the current protected area network preserves very little of the most biodiverse areas and does not meet conservation targets as determined by the South African National Biodiversity Institute. The 2013 Limpopo Conservation Plan models critical biodiversity and ecological support areas on a coarse scale and assesses protection levels of the various habitats indicating that protected areas in Limpopo need to be increased by an additional 85% of the current network. Serious threats to the integrity of the Vhembe Biosphere Reserve arise from planned large scale coal mining and a largely rural population developmentally constrained by Apartheid settlement patterns. Given the prioritisation of economic development by local and provincial government and a rapidly transforming environment, there is an urgent need to refine biodiversity and eco-system services data to prioritise future conservation areas in terms of biosphere zonation, emphasizing connectivity between these, coupled with innovative, endogenous, strategies for establishing and managing them.