The ranoid family Pyxicephalidae is an endemic group of African frogs, with the majority of its diversity concentrated in South Africa. Here we present the first molecular phylogeny that includes as many as nine of the ten pyxicephalid genera, omitting only Nothophryne, based on four nuclear gene fragments and one mitochondrial gene fragment. This study corroborates the basal placement of Pyxicephalus and Aubria, and the sister group placement of Natalobatrachus and Arthroleptella, which were first signalled using smaller datasets. The evolution of endotrophic development has evolved twice within the Pyxicephalidae, once in the ancestor of Anhydrophryne, and independently in the ancestor of Arthroleptella. The implications for the evolution of body size, from the large species in Pyxicephalus and Aubria to the smallest pyxicephalid species in Arthroleptella and Microbatrachella are discussed.