We present a molecular phylogeny of 26 out of the 28 currently accepted genera in the subfamily Chrysophylloideae (Sapotaceae)using parsimony, parsimony jackknifing, and Bayesian inference. A data matrix of 8984 characters was obtained from DNA sequences of seven chloroplast loci, two nuclear loci, indels coded as binary characters, and morphology. Our phylogenetic reconstruction suggests that Chrysophyllum, Pouteria, and Pradosia, as well as some sections within Chrysophyllum and Pouteria, are all polyphyletic. These taxa were previously described largely on the basis of unique combinations of states for a set of morphological characters. Mapping some of these characters onto one of the most parsimonious trees indicates that the symplesiomorphic flower in the subfamily was probably 5-merous, had stamens inserted in the tube orifice, staminodes, seeds with foliaceous cotyledons, exserted radicle, and endosperm. These characters have subsequently been lost multiple times and cannot be used as synapomorphies to support broad generic concepts. Despite the high degree of homoplasy some well-defined clades can be described on the basis of alternative character state combinations. Also, many of these well-supported clades appear to be restricted to particular geographical areas (e.g. all taxa in Australasia form a monophyletic group). Hence, we suggest that the segregate genera Aningeria, Malacantha, and Martiusella may ultimately be resurrected, and probably also Donella and Gambeya, but their circumscriptions are still unclear. One species, Chrysophyllum cuneifolium, may have originated from a hybridization event between continents where the maternal genome (cpDNA) comes from South America and the nuclear genome comes from Africa.