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The biosphere reserve model is a global designation in accordance with UNESCO’s Man and the Biosphere Programme. Biosphere reserves are required to fulfil three functions as prescribed by UNESCO, namely conservation, sustainable development and logistic support. Worldwide, the 669 biosphere reserves in 120 countries are experiencing different degrees of effectiveness in fulfilling these functions. This paper investigates trends in the selection of sites for new biosphere reserves and puts forward a set of criteria for the establishment of future biosphere reserves in South Africa, in order to capitalize on the potential of the MAB Programme. Given the country’s limited natural, economic and social resources, there is a need to prioritize where these resources could best be allocated. Presently, new sites for biosphere reserves in South Africa are randomly nominated, resulting in biosphere reserves that are not always optimally located. The proposed suite of biosphere reserve criteria for South Africa has the potential to be of valuable assistance in selection processes for future effective and efficient biosphere reserves that will proudly earn their rightful place in the South African landscape. The criteria are structured according to four subsections, namely a general section that addresses national matters of general concern to the MAB Programme, and three sections covering the three biosphere reserve functions. These criteria also have the potential to be adapted to the needs of other developing countries in support of the effective implementation of the MAB Programme.