The stapeliads of the Ceropegieae (Apocynaceae-Asclepiadoideae), are approximately 340 species of stem-succulents placed in around 30 genera, found in semi-arid parts of the Old World. Here we sampled 192 species (i.e. nearly two thirds of the total) from across the full geographic range of the group and analysed data from the two nuclear regions (nuclear ribosomal ITS and ncpGS) and five plastid regions (psbA-trnH intergenic spacer, rps16 intron, trnL-trnF intergenic spacer, trnS-trnG intergenic region and the non-coding rpl32-trnL region). We find that the stapeliads radiated first in the northern hemisphere from Africa to southern Europe and Myanmar. This radiation subtends a grade of minor clades in the south-western corner of the African continent. These were followed by a single clade containing major radiation back across Africa from South Africa to tropical Arabia (but no further east than Dhofar, Oman), which includes also a single early spread into Madagascar. We establish the monophyly of many of the genera, such as Echidnopsis Hook.f., Hoodia Hook., Huernia R. Br., Piaranthus R. Br., Rhytidocaulon P.R.O. Bally and Tridentea Haw., but find that Duvalia Haw., Orbea Haw., Stapelia L. and Tromotriche Haw. are polyphyletic. We show that in certain vegetative features, there is broad cohesion across clades. Florally, on the other hand, the stapeliads exhibit considerable plasticity and we are able to show that very differently shaped flowers as well as large and small flowers evolved repeatedly among closely related species.