Bioprospecting has yielded multiple drugs approved by the FDA to treat various forms of cancer including vincristine and vinblastine isolated from the Madagascar periwinkle Catharanthus roseus (Apocynaceae). Vincristine and vinblastine are drugs of choice for the treatment of pediatric leukemia. Taxol, a drug marketed by Bristol-Meyers Squibb, is used to treat ovarian and breast cancer. Taxol was isolated from the Pacific yew tree Taxus brevifolia (Taxaceae) during a systematic search by the National Cancer Institute. Currently, Lars Bohlin at Uppsala University and Samantha Gerlach at Tulane University are studying cyclotides, small cyclic peptides from the Violaceae and Rubiaceae, as a new category of biodiversity derived anticancer compounds. Bioprospecting of orthologous genes from a wide array of plant species offers a valuable alternative to protein engineering and directed evolution. While enzyme variants corresponding to any enzymatic step within a target pathway can be screened to enhance catalytic efficiency, pathway bottlenecks present the most promising opportunities for enzyme bioprospecting.