Photosynthetic pathway innovations have had a large impact on patterns of diversification of angiosperm lineages and the biogeographic distribution of ecological assemblages. C₄ photosynthesis has been one of the most studied processes in plants with respect to function, structure, occurrence, and response to climatic conditions. One of the most promising areas of research of C₄ photosynthesis is in the Cleomaceae. Here we explore the phylogenetic origins of the C₄ pathway in the Cleomaceae using maximum parsimony, maximum likelihood, and Bayesian inference analyses of nrDNA ITS sequences. As has been found previously, commonly recognized genera including Buhsia, Cleomella, Dactylaena, Gynandropsis, Isomeris, Oxystylis, Podandrogyne, Polanisia, and Wizlizenia are derived from within a paraphyletic Cleome. The phylogenetic results presented here indicate that there are likely at least five separate origins of carbon concentrating mechanisms in the Cleomaceae, including at least three separate origins of C₄ species. Analyses of historical biogeography suggest Cleomaceae originated in central Asia.