The Chromodorididae is a large and colourful family of nudibranch sea slugs distributed across the world’s oceans. Most diversity is centred in the Indo-Pacific, but several genera are present in multiple ocean basins, or across regions separated by biogeographical barriers. The monophyly of these widespread genera had not been tested previously. We used 18S rDNA, 16S rDNA and COI sequence data to generate a molecular phylogeny for this group. We recovered evidence of paraphyly or polyphyly in all of the widespread genera examined (Hypselodoris, Mexichromis, Chromodoris and Glossodoris). East Atlantic Hypselodoris and west Atlantic + east Pacific Mexichromis species were more closely related to each other than they were to their Indo-Pacific congeners. The addition of Southern Ocean species of Digidentis demonstrated an interesting alternative to this relationship, becoming the sister group for the east Atlantic Hypselodoris on the basis of 16S and 18S data, but not COI data. Sister group relationships were recovered for most monotypic or enigmatic genera. Ardeadoris is linked to Glossodoris, as is Diversidoris; Pectenodoris is sister to the Indo-Pacific Mexichromis clade, and Verconia is the sister to Noumea haliclona. Controversy surrounding the placement of the three most basal genera was only partially resolved. Using Actinocyclus to root the mitochondrial trees, Cadlinella was the unsupported sister to the Chromodorididae (excluding Cadlina), and Tyrinna occupied a relatively basal position, although this also did not receive significant statistical support. Adding nuclear 18S data gave support for Cadlina as the sister group to the rest of the Chromodorididae s.s. Otherwise, like previous molecular studies, mitochondrial genes supported an alternative position for Cadlina (with other dorid genera).