Phylogenetic relationships among angelfishes (Pomacanthidae) and their putative sister taxon, the butterflyfishes (Chaetodontidae), were examined using 12S and 16S mitochondrial DNA sequences. ML and MP trees were highly congruent with good basal resolution. Monophyly of the two families was supported, although a clade comprising the Chaetodontidae and one of the outgroups, the Scatophagidae, formed the sister clade to the Pomacanthidae. All genera and subgenera within the Pomacanthidae were examined. The relationships among the 24 representative species were consistent with traditional generic boundaries, with the exception of the genus Centropyge, but differed from previous phylogenies. Estimated ages of divergence based on trans-isthmian pairs were compared with independent fossil evidence. Trans-isthmian estimates were highly conservative, while fossil-calibrated estimates were most consistent with available evidence. Fossil calibrated estimates suggest that the family has been impacted by both the Terminal Tethyan Event and the closure of the Isthmus of Panama. Within the family, ecological diversity and species-level diversification are restricted primarily to a single pygmy angelfish clade with an origin near the Oligocene-Miocene boundary.