Jamesbrittenia is a genus of 84 largely perennial sub-shrubs and herbs with a wide distribution in southern Africa (except J. dissecta in Sudan, Egypt and India). Plastid (rps16 and psbA-trnH) and nuclear (GScp) sequences were obtained for 42 species, mostly from the arid winter-rainfall west and southern regions of southern Africa. Applying both parsimony and Bayesian inference to combined molecular and morphological data sets, a phylogenetic hypothesis which is robust at the deeper nodes, was produced. This supports the monophyly of Jamesbrittenia, and also indicates the early divergence of J. ramosissima and three major clades.