The phylogenetic relationships of the skunks to the Mustelidae and other caniform carnivores were examined using mitochondrial-DNA (mtDNA) sequence data from portions of the 12S and 16S ribosomal RNA (rRNA) genes. Data were combined with partial sequences of the cytochrome b gene and morphological data obtained from the literature, and used in a total-evidence analysis. The Mustelidae represented a paraphyletic group, with the skunks (Conepatus, Mephitis, and Spilogale) and the Oriental stink badger (Mydaus) forming a monophyletic clade separate from a clade containing the rest of the Mustelidae and the monophyletic Procyonidae. Within the Mustelidae, minus the skunks and stink badger, only one currently recognized subfamily, the Lutrinae, represented a monophyletic group. The families Phocidae, Otariidae, and Odobenidae formed a monophyletic group that was the sister group to the clade composed of the skunks, procyonids, and mustelids. The families Ursidae and Canidae occurred at the base of the Caniformia clade. It is proposed that the skunks be elevated to the level of family and be referred to as the Mephitidae. The family Mephitidae includes the genera Mephitis (striped and hooded skunks), Conepatus (hog-nosed skunks), Spilogale (spotted skunks), and Mydaus (Oriental stink badgers).