Approximately 8% of calyptrate species diversity comes from the Calliphoridae, which includes flies of medical, veterinary, and forensic importance. The status of family Calliphoridae has for years been the central systematic problem of the superfamily Oestroidea, and phylogenetic relationships between the key groups of the Calliphoridae are unresolved and controversial. We reconstructed phylogenies of the Calliphoridae within the larger context of the other Oestroidea based on 5,189 bp of combined data from one mitochondrial (cytochrome oxidase subunit one) and three nuclear (carbamoylphosphate synthetase, elongation factor one alpha, and 28S ribosomal RNA) genes using maximum parsimony, maximum likelihood, and Bayesian methods. Trees obtained from the different phylogenetic methods were almost identical. Calliphoridae is polyphyletic, with the phylogenetic position of Mesembrinellinae still uncertain but clearly outside the lineage that includes other Calliphoridae and some noncalliphorids, and Polleniinae is the sister group of the family Tachinidae. Strong support for a sister group relationship between Rhiniinae and traditional calliphorid subfamilies conflicts with a recent proposal to give Rhiniinae family status. All calliphorid subfamilies (except Calliphorinae) for which we had more than one species were monophyletic. Melanomyinae was nested within Calliphorinae. Toxotarsinae was more closely related to Calliphorinae rather than, as indicated by morphology, to Chrysomyinae. Efforts to resolve the relationships of the Oestroid families were largely inconclusive, although the monophyly of the superfamily was strongly supported.