Identification of agents that are pharmacologically active against human cancer has depended largely on the screening of natural products and their analogs. Many anticancer drugs have been discovered fortuitously through random investigation of organisms; indeed, serendipity remains important in anticancer drug discovery. Although it is broadly accepted that cancers comprise an evolutionary microcosm, this idea has not been advanced to understand and control carcinogenic progression. Here, we address anticancer drug discovery from an evolutionary perspective and present a series of case studies that demonstrate that the rate of anticancer drug discovery can be increased greatly by targeted screening of natural compounds from ancient species.