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. Drugs that target oncogenes have shown to be effective in the treatment of some cancers. 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 or terminal differentiation. However, in other cases, oncogene inactivation results in the apparent loss of the neoplastic properties of tumor cells, that now appear and behave like normal cells, however, upon oncogene reactivation rapidly recover their neoplastic phenotype. These observations illustrate that oncogene inactivation can result in a state of tumor dormancy. Understanding when and how oncogene inactivation induces sustained tumor regression will be important towards the development of successful therapeutic strategies for cancer.