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Plant metabolites have been the successful source of drugs and provided considerable value not only to the pharmaceutical industry but also to human health problems. Although pharmaceutical companies significantly decreased their activities in natural product discovery during the past few decades, various multidisciplinary approaches have been made to create new opportunities for finding innovative plant derived pharmaceuticals in post-genome era. Strategies to integrate the knowledge on medicinal plants into rational drug screening, the unique biodiversity of plant metabolites into random drug screening, and the chemical diversity of plant metabolites into combinatorial chemistry have been reviewed with concrete examples. Innovative biotechnologies in plant cell and tissue cultures, and the latest achievements in metabolic engineering and genetic modification should significantly improve the production sustainability and efficiency of plant-derived pharmaceuticals.