The worldwide botanical and medicinal culture diversity are astonishing and constitute a Pierian spring for innovative drug R&D. Here, the latest awareness and the perspectives of pharmacophylogeny and pharmacophylogenomics, as well as their expanding utility in botanical drug R&D, are systematically summarized and highlighted. Chemotaxonomy is based on the fact that closely related plants contain the same or similar chemical profiles. Correspondingly, it is better to combine morphological characters, DNA markers and chemical markers in the inference of medicinal plant phylogeny. Medicinal plants within the same phylogenetic groups may have the same or similar therapeutic effects, thus forming the core of pharmacophylogeny. Here we systematically review and comment on the versatile applications of pharmacophylogeny in (1) looking for domestic resources of imported drugs, (2) expanding medicinal plant resources, (3) quality control, identification and expansion of herbal medicines, (4) predicting the chemical constituents or active ingredients of herbal medicine and assisting in the identification and determination of chemical constituents, (5) the search for new drugs sorting out, and (6) summarizing and improving herbal medicine experiences, etc. Such studies should be enhanced within the context of deeper investigations of molecular biology and genomics of traditional medicinal plants, phytometabolites and metabolomics, and ethnomedicine-based pharmacological activity, thus enabling the sustainable conservation and utilization of traditional medicinal resources.