Over the past decades, there has been an encouraging increase in survival after solid organ transplantation. However, with longer life spans, more transplant recipients are at risk of dying with functioning grafts from illnesses such as cancer and cardiovascular conditions. Malignancy has emerged as an important cause of death in transplant recipients and is expected to become the leading cause of death in transplanted patients within the next decade. While it is known that solid organ transplant recipients have a three to five-fold increased risk of developing cancer compared with the general population, the mechanisms that lead to the observed excess risk in transplant recipients are less clear. This review explores the etiology of the increased cancer incidence in solid organ transplant including the effect of immunosuppressants on immunosurveillance and activation of oncogenic viruses, and carcinogenic effects of these medications; the role of chronic stimulation of the immune system on the development of cancer; and the impact of pre-existing cancer risk factors and factors related to end-stage organ disease on the cancer excess incidence in solid organ transplant recipients.