Melastomataceae are among the most abundant and diversified groups of plants throughout the tropics, but their intrafamily relationships and morphological evolution are poorly understood. Here we report the results of parsimony and maximum likelihood (ML) analyses of cpDNA sequences from the rbcL and ndhF genes and the rpl16 intron, generated for eight outgroups (Crypteroniaceae, Alzateaceae, Rhynchocalycaceae, Oliniaceae, Penaeaceae, Myrtaceae, and Onagraceae) and 54 species of melastomes. The sample represents 42 of the family’s currently recognized ~150 genera, the 13 traditional tribes, and the three subfamilies, Astronioideae, Melastomatoideae, and Memecyloideae (= Memecylaceae DC.). Parsimony and ML yield congruent topologies that place Memecylaceae as sister to Melastomataceae. Pternandra, a Southeast Asian genus of 15 species of which five were sampled, is the firstbranching Melastomataceae. This placement has low bootstrap support (72%), but agrees with morphological treatments that placed Pternandra in Melastomatacaeae because of its acrodromal leaf venation, usually ranked as a tribe or subfamily. The interxylary phloem islands found in Memecylaceae and Pternandra, but not most other Melastomataceae, likely evolved in parallel because Pternandra resembles Melastomataceae in its other wood characters. A newly discovered plesiomorphic character in Pternandra, also present in Memecylaceae, is a fibrous anther endothecium. Higher Melastomataceae lack an endothecium as do the closest relatives of Melastomataceae and Memecylaceae. The next deepest split is between Astronieae, with anthers opening by slits, and all remaining Melastomataceae, which have anthers opening by pores. Within the latter, several generic groups, corresponding to traditional tribes, receive solid statistical support, but relationships among them, with one exception, are different from anything predicted on the basis of morphological data. Thus, Miconieae and Merianieae are sister groups, and both are sister to a trichotomy of Bertolonieae, Microlicieae + Melastomeae, and Dissochaeteae + Blakeeae. Sonerileae/Oxysporeae are nested within Dissochaeteae, Rhexieae within Melastomeae, and African and Asian Melastomeae within neotropical Melastomeae. These findings have profound implications for our understanding of melastome morphological evolution (and biogeography), implying, for example, that berries evolved from capsules minimally four times, stamen connectives went from dorsally enlarged to basal/ventrally enlarged, and loss of an endothecium preceded poricidal dehiscence.