Phylogenetic analyses of Isodon and related genera using the nuclear ribosomal internal transcribed spacer (nrITS), cpDNA regions (trnL—trnF region and rps16 intron), and morphological data are presented. The results clarify the relationships among Isodon and its putative related genera and the question of the monophyly of Isodon and its relationship with Siphocranion. Siphocranion is a monophyletic genus and the sister clade to the remaining species; the new subtribe Siphocranioninae of tribe Ocimeae is described to accommodate it. Isodon, as currently circumscribed, is only monophyletic if Skapanthus oreophilus is included in it. Isodon forms a distinct subtribe Isodoninae within tribe Ocimeae and three strongly supported subclades are identified within the genus. In addition, a close relationship between Hanceola and Hyptis is indicated in the combined nrITS cpDNA data set with Bayesian inference and this is also supported in morphological analyses, but more studies are needed to confirm this relationship. It is evident that subtribe Hanceolinae is polyphyletic as currently defined, so subtribe Hanceolinae is restricted to accommodate Hanceola alone. The relationships between Isodon and other genera within tribe Ocimeae are still unresolved; the newly erected subtribe Isodoninae is a monophyletic group representing a distinct lineage in subtribe Ociminae. The relationships among the species of the largest subclade C of Isodon are still poorly known. Additional studies of this group with additional data and more intensive taxon sampling might help to resolve these issues.