The moment the health team applies therapy to a patient’s cancer it is game on, unless the therapy results in cure. The surviving cancer cells will evolve and what emerges from the cancer cells is often worse and even more fatal than the original states of the cancer cells. Hence, wittingly or unwittingly the health team engages in an evolutionary game with the patient’s cancer cell populations. Current practice targets the cancer’s present ecological (size and distribution of cancer cell populations) and evolutionary (heritable composition of the cancer cells) states. The health team begins as the leader in the therapy game, but soon becomes the follower as subsequent lines of therapy “chase” the cancer’s resistance evolution. Better for the health team to remain the leader. Stackelberg evolutionary game theory aims to do just that in any context where one is managing evolving resources, pests, diseases or cancer. Such games aim for evolutionarily enlightened strategies where, in the case of cancer, the oncologist incorporates both the ecological and evolutionary dynamics into a decision tree for when to switch therapies (or even stop therapies) in response to the past, present and possible future states of the cancer.