The development of malignancy in immunosuppressed organ transplant recipients has recently gained increasing attention. Increased awareness of this problem has come from recent data indicating that vascular disease and cancer are the leading causes of death in transplant recipients. Despite the realization of this fact, few efforts have been made to thwart deaths due to cancer in transplant recipients. However, now that many transplant recipients maintain their organ allografts for decades, the risk for cancer is increasing even more, exposing a need for possible solutions. Fundamentally, transplant recipients are at a high risk for cancer because the immunosuppressive drugs used in their treatment regimen suppress immune reactivity against arising cancer cells. Some of these drugs directly impede DNA repair, induce cancer cell aggressiveness, and promote tumor angiogenesis. In situations where cancer has developed in transplant recipients, one potential action is to reduce their daily immunosuppression. In some cases immunosuppression minimization can reduce tumor growth or even result in tumor regression, but the threat of rejection increases substantially. Another possible solution is to move toward mammalian target of rapamycin (mTOR)-based immunosuppression, use of which has been experimentally demonstrated to have both immunosuppressive and potent anticancer effects. Clinical studies are presently underway to test this idea, which could help to alleviate the problem of cancer in transplant recipients. In this overview, the topic of cancer in transplant recipients will be addressed, as well as new approaches to reduce this increasingly recognized problem in transplantation.