The Pachydactylus serval and weberi groups constitute a clade of small to moderate sized (typically 40–50 mm SVL), mostly rupicolous geckos that are distributed widely in western South Africa and Namibia, with scattered populations in eastern Namibia and adjacent northwestern Botswana. The taxonomic status of many of the described members of these groups has long been unresolved, and numerous subtly divergent populations have been identified since the last revisionary work was undertaken. Examination of more than 1800 specimens referable to these species groups permits recognition of at least 21 species, clearly divisible into serval and weberi subclades. Within these clades, most species are highly morphologically conservative, although there are diagnostic differences in a number of characters, most notably juvenile color pattern. The species boundaries so revealed are supported by phylogenetic evidence from the cytochrome b mitochondrial gene. The validity of the currently recognized species in the P. serval/weberi clade (P. serval, P. weberi, P. fasciatus, P. tsodiloensis, P. waterbergensis) is confirmed, and the taxa P. purcelli, P. acuminatus, P. werneri are elevated from synonymy or subspecific rank to full species. Pachydactylus robertsi, recently removed from the synonymy of P. scutatus, and P. kobosensis are confirmed as valid members of the P. weberi group. Pachydactylus sansteynae, originally described as a subspecies of P. serval, is a valid species but is not a member of P. serval/weberi clade. Pachydactylus montanus is a senior subjective synonym of P. onscepensis and is raised from the synonymy of P. serval. A genetically diverse taxon, P. montanus may include more than one biological species. In addition, eight new species are described and the existence of two additional taxa, each currently known from limited material, is noted. The areas of greatest diversity for the clade as a whole are along the lower Orange River and in southern Namibia. Both the Richtersveld/ Hunsberg region in the west and the Karasberge in the east harbor at least five species in the P. serval/weberi clade. The evolutionary history of the group is probably associated with the fragmentation of rocky substrates and the historical isolation of some regions by changing paleopositions of the drainage of the Orange River. Distribution patterns of geckos in this clade are coincident with those of cordylids and scorpions and together, these groups — all of which have explicit hypotheses of relationships — provide a possible basis for a fine-scaled  biogeographic analysis of western portions of the southern African subcontinent. Keywords: Gekkonidae, Pachydactylus, systematics, Namibia, South Africa, molecular phylogeny, biogeography.