Lepechinia (Lamiaceae subf. Nepetoideae) is a New World genus composed of about 42 species distributed primarily from Northern California to Central Argentina. Previous morphological and molecular studies on Lepechinia have raised questions on the monophyly of the genus and its placement within the tribe Mentheae. In this paper the phylogenetic placement and monophyly of Lepechinia is examined within the context of the tribe Mentheae using cpDNA (ycfl and trnL-F) and nrDNA (ITS and ETS) markers. Melissa is shown to be sister to Lepechinia in both cpDNA and nrDNA analyses, and the monotypic genera Chaunostoma and Neoeplingia are found to be embedded within Lepechinia. The subtribe Menthinae is shown to be paraphyletic, with several genera needing to be reassigned. In particular, Neoeplingia should be included within the subtribe Salviinae. The genera Heterolamium and Melissa, both previously unplaced with regard to subtribe, are now clearly assigned to the subtribes Nepetinae and Salviinae, respectively. The cpDNA marker ycfl has great phylogenetic utility, and is shown to be 50% more informative than trnL-F for the taxa used in this study.