The phylogeny of Celastraceae subfamilies Cassinoideae (120 species in 17 genera in both the Old and New World tropics and subtropics) and Tripterygioideae (39 species in seven genera) was inferred using plastid (matK, trnL-F) and nuclear (ITS and 26S rDNA) loci together with morphological characters. Subfamily Cassinoideae include those Celastraceae genera with drupes, berries, or nuts that have one to five locules and one to two seeds per locule, while Tripterygioideae include those genera with one to two seeded samaras that lack arillate seeds. We infer that both subfamilies are grossly polyphyletic groups, with Cassinoideae consisting of ≥ eight separate lineages and Tripterygioideae consisting of ≥ six separate lineages. Crossopetalum, from tropical America, is part of an early derived lineage sister to a taxonomically diverse Austral-Pacific clade. Myginda is not distinct from Crossopetalum. Gyminda Orthosphenia Rzedowskia Schaefferia are a clade that is only distantly related to Crossopetalum. The monotypic Hartogiopsis is in a clade with other Madagascan genera and sister to the more widely distributed Pleurostylia. Fraunhofera and Plenckia are a clade nested within New World Maytenus; taxonomic changes are required for ≥ one of these genera. Platypterocarpus is part of a primarily African clade and is only distantly related to Tripterygium and Wimmeria.