Mathewsia (6 spp) and Schizopetalon (10 spp) are sister genera of the tribe Schizopetaleae (Brassicaceae, Cruciferae). The genera are mostly endemic to Chile and neighboring areas of Peru and Argentina, with most species growing in the hyperarid Atacama Desert and adjacent areas. This geographic distribution and the presence of different life forms in Mathewsia (perennial) and Schizopetalon (annual) provide the opportunity to compare patterns of diversification under extreme environmental pressure. In this paper, phylogenetic relationships are estimated for 17 species using a combination of two nuclear regions (rDNA ITS+ETS) and four plastid regions (atpI-atpH, trnQ-rps 16, trnH-psbA spacers, and rps16 intron) using maximum parsimony, maximum likelihood, and Bayesian approaches. Analyses of the combined cpDNA and the combined nrDNA result in topologies that are highly similar, although several instances of topological incongruence are noted. Results from all three criteria and all datasets support the monophyly of Schizopetalon, but not of Mathewsia. Mathewsia is rendered non-monophyletic because M nivea is placed outside of Schizopetaleae (Mathewsia+Schizopetalon); a result that is also supported by morphology. The monophyly of some species is confirmed; however, several currently recognized species were not recovered as a clade and will require additional study. Further analyses are needed to resolve the placement of M nivea and the origins of discordant nuclear and plastid signal.