Understanding how species diversify and evolve in species-rich areas like the lowland rain forest in the Neotropics is critical for conservation in times of unprecedented threats. To determine how the Andean uplift, the formation of the Panama land bridge, and Pleistocene climatic fluctuations affected dispersal and diversification in the Sapotaceae subfamily Chrysophylloideae, we collected 146 Chrysophylloideae accessions in previously under-explored areas, generating one of the most geographically complete data sets for neotropical Sapotaceae. Sapotaceae is a good model to test diversification hypotheses in lowland neotropical rain forests as it predominantly occurs <1000 m altitude, and it is an abundant and species-rich group in this biome. We generated a time calibrated phylogeny of 123 Sapotaceae species based upon the nuclear ribosomal internal transcribed spacer region that suggests migration between lineages to the east and the west Andean Cordilleras occurred before and after periods of major uplift, indicating that the Andes did not represent a significant barrier to dispersal for Sapotaceae, although it may have promoted vicariance in some cases. Dispersal between South and Central America occurred mainly prior to the formation of the Panama land bridge, suggesting that this event did not affect migration patterns in Chrysophylloideae. We inferred diversification rates and detected three shifts in the phylogeny, but they are not congruent with tectonic movements during the middle Miocene and climatic changes during the Pleistocene. Finally, some species with restricted distributions appear to be phylogenetically nested within species with broader ranges, suggesting ancestor descendent relationships and insights into patterns of speciation in rain forest trees.