Malignancy is a well defined complication of chronic immunosuppression. Post transplant malignancies appear to be related to cumulative doses of immunosuppression, and in pediatric patients, acute infection of previously naive patients. The most commonly encountered malignancy in this age population is Post Transplant Lymphoproliferative Disorder (PTLD). PTLD is not a single entity but rather represents a continuum of disease. Treatment of PTLD should be initiated with immunosuppression reduction. Standard dose chemotherapy leads to significant morbidity. With the introduction of anti-CD20 antibody treatment with rituximab, chemotherapy has become second line therapy. The occurrence of solid malignancy appears to be associated with chronic immunosuppression. These cancers include those of skin, gynecologic organs, and the rectum, all of which appear to have the strongest association with viral mediators. Several strategies have been postulated to minimize the occurrence of malignancy. These include ganciclovir prophylaxis for the prevention of PTLD and the use of mychophenolic acid and TOR inhibitor maintenance to diminish the incidence of PTLD and solid malignancies. This leaves transplant physicians with several new and novel immunosuppressive agents with uncertain oncologic potentials that will need to be examined over the next decade.