Phylogenetic relationships within Sapindaceae sensu lato are assessed using sequence data from two plastid genes, analyzed separately and together. A total of 46 rbcL sequences (31 of which are new), and 89 matK sequences (75 new) representing 64 genera were subjected to parsimony and Bayesian analysis. The results support three major lineages, relationships between which are only weakly supported. Xanthoceras sorbifolium is not clearly a member of any of these lineages, and there is some support for it being the first lineage to diverge within the entire assemblage. Support for a broadly defined Sapindaceae incorporating Aceraceae, Hippocastanaceae, and Xanthoceras is very robust. A division into four subfamilies is proposed: Sapindoideae (including Koelreuteria and Ungnadia); Hippocastanoideae (including taxa previously referred to Aceraceae and Hippocastanaceae, plus Handeliodendron); a more narrowly defined Dodonaeoideae; and a monotypic Xanthoceroideae. Tribal groupings are critically evaluated in light of the analyses. Although many of the current tribes appear paraphyletic or polyphyletic, there is support for the monophyly of some core groups of genera that suggest realignments of tribal concepts that would render them more informative of relationships.