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Sandwiched between the Namib and Kalahari Deserts of southwestern Africa are the karooid and escarpment biotopes of Namibia which are rich in endemics of many taxa. Most plant, invertebrate, amphibian, reptile, mammal and bird species endemic to Namibia are found in a zone running through, and to the west of, Namibia’s escarpment region. There is also an important region of endemism for succulent plants, reptiles and invertebrates in the Succulent Karoo biome. Congruence between endemism hotspots, particularly on rocky substrates, is remarkably high for most taxa, implying broadly similar speciation processes. Possible speciation mechanisms in different parts of the country include the spatial isolation of rupicolous taxa such as insects and reptiles by the formation of large coastal dune fields; the expansion and contraction of wooded savannas during pluvial and interpluvial periods; and global temperature shifts which created highland refugia for frost-susceptible plants and poikilotherms. Areas of endemism and species richness overlap poorly for Namibia’s mainly arid-dwelling endemic vertebrates, as richness is highest in the mesic wetlands and woodlands of northeast Namibia. The overlap for succulent plants, insects and arachnids, however, is relatively high. Centres of endemism for plants and vertebrates fall mainly outside protected areas, as few parks were established with biodiversity indices in mind. Our analysis of endemism congruence, provides a strong platform for the promulgation of new protected areas to safeguard Namibia’s unique biota. Furthermore, analysis of speciation patterns and processes is a useful predictive tool for the identification of other biotically important sites.