Trichostema (Lamiaceae) is a North American genus comprising five sections and 18 species. Phylogenetic relationships were inferred using DNA sequences (ITS, ndhF) and morphology (63 characters). The monophyly of Trichostema is well supported in four analyses (ITS, ndhF, ITS ndhF, ITS ndhF morphology), but not in the analysis based on morphological data alone. In all analyses, the monophyly of sections Chromocephalum and Trichostema is well supported. The monophyly of section Paniculatum is moderately supported, and there is conflicting evidence regarding the monophyly of section Orthopodium. Although DNA data alone suggest that T. brachiatum is not a member of section Orthopodium, its retention in section Orthopodium is equivocal in the combined DNA-morphology analyses. The submerging of the monotypic section Rhodanthum into Paniculatum by Lewis and Rzedowski is not adopted because the monophyly of this grouping is poorly supported. Biogeographic history and character evolution (life history and chromosome number) are explored in the context of the phylogeny based on the combined ITS and ndhF sequence data.