Following the genesis of a cancer clade within the host, tumor cells rapidly undergo divergent evolution to form multiple cancer species. Evolvability itself is one trait produced in this initial expansion and "speciation" event, lending cancer cells the capacity to adapt to changing environmental stimuli and selection pressures. The cover depicts the natural history of a cancer, from establishment of the initial malignant cell through speciation and "extinction events" as successive rounds of therapy are applied. In their review, Pienta and colleagues argue that the acquisition of evolvability and lethality are examples of convergent evolution that occur in all lethal cancers. These events precede any exposure to therapy, and thus render highly evolvable tumor species that are inherently resistant to therapy by virtue of their adaptability. The authors argue that the future of clinical cancer management must account for this early event in the natural history of cancer and adapt to it in order to more effectively impede the progression of lethal disease. For more information, please see the article on page 801. (Illustrations: Tim Phelps ©2019 JHU AAM; Department of Art as Applied to Medicine; The Johns Hopkins University School of Medicine).