Cancer is caused by genetic changes that activate oncogenes or inactivate tumor suppressor genes. The repair or inactivation of mutant genes may be effective in the treatment of cancer. Indeed, drugs that target oncogenes can be effective in the treatment of cancer. However, it is still unclear why the inactivation of a single cancer-associated gene would ever result in the elimination of tumor cells. In experimental transgenic mouse models the consequences of oncogene inactivation depend upon the genetic and cellular context. In some cases, oncogene inactivation results in the elimination of all or almost all tumor cells through apoptosis by the phenomenon described as oncogene addiction. In other cases, oncogene inactivation predominantly results in the terminal differentiation or cellular senescence of tumor cells. In yet others, oncogene inactivation results in the apparent loss of the neoplastic properties of tumor cells, which now appear and behave like normal cells; however, upon oncogene reactivation at least some of these cells rapidly recover their neoplastic phenotype. Thus, oncogene inactivation can result in a state of tumor dormancy. Hence, understanding when and how oncogene inactivation induces apoptosis, differentiation, and senescence within a tumor will be important when developing effective strategies for the treatment of cancer.