Epstein-Barr virus (EBV) is associated with a variety of malignancies including post-transplant lymphoproliferative disease (PTLD). These include B and T cell lymphomas, epithelial, and mesenchymal tumors. The virus is ubiquitous, transmitted in saliva, and not usually associated with the development of malignancy. PTLD is usually associated with EBV when it occurs soon after the transplant. Measurement of viral DNA in blood, especially plasma, may be useful in the diagnosis of PTLD. Treatment approaches include withdrawal of immunosuppression, monoclonal antibodies or antibody conjugates, cytotoxic chemotherapy, and a variety of virus-specific treatments such as adoptive cellular therapy with EBV-specific T cells. Approaches to prevention include selection of immunosuppressive regimens that minimize the risk. In the future, EBV vaccines may be available for potential transplant recipients.