Major drainage divides in southern Africa are interpreted to reflect lines of epeirogenic flexuring of the subcontinent associated with the formation of co-related basins. The Great Escarpment, which separates coastal and inland drainage systems, marks the locus of the Escarpment axis. It was initiated by Early Cretaceous rift flank uplift associated with the break-up Gondwana. Geophysical studies suggest that subsequent erosion, coupled with sedimentation on the continental shelf, would have resulted in progressive inland migration of this flexure. The divide between the Orange-Vaal River system and the Limpopo and Molopo-Nossib-Auob drainage basins is designated the Etosha-Griqualand-Transvaal (EGT) axis. Upper Cretaceous flexuring along this axis disrupted old drainage lines, and initiated deposition of the Kalahari formation. The end-Cretaceous Ovamboland-Kalahari-Zimbabwe (OKZ) axis forms the watershed between the Zambezi and Limpopo Rivers in Zimbabwe, and separates the latter river system from fossil endoreic drainage lines in the Kalahari, which originally emptied into the Makgadigadi Pans system. In the south of Botswana, this axis is defined by the Kalahari Schwelle, which separates the fossil Kalahari drainages from the Molopo-Nossib River system. Processes responsible for initiating the EGT and OKZ flexures are poorly understood. However, the inferred ages of both these two axes and the Escarpment axis correspond with episodes of alkaline volcanism in southern Africa. This argues for a link between continental flexuring and volcanic activity. Major Pliocene uplift occurred along a line intermediate between the Great Escarpment and the present coastline in the east of the country (the Ciskei-Swaziland axis). More subdued Plio-Pleistocene flexuring along a southwest-northeast axis (designated the Bushmanland-Harts axis) traversing the interior of South Africa was responsible for the formation of major pans ("floors") in Bushmanland and the Orange Free State. There are a number of subordinate lines of uplift (the Khomas, Otavi, and Zoutpansberg axes) which are parallel to the Bushmanland-Harts axis. They are presumably related to the same stress field, and thus probably of similar age. These latter axes are all subparallel to active faults in northern Botswana which are interpreted to reflect southwestwards migration of the east African rift system, following lines of structural weakness. Sequential uplift along the axes which have been identified provides a framework for interpreting the evolution of drainages and erosion surfaces on the sub-continent.