Uncontrolled expansion of donor-derived Epstein-Barr virus (EBV)-infected B cells has become a significant problem in recipients of allogeneic hematopoietic stem cell transplantations. Major risk factors for the early development of posttransplantation lymphoproliferative disease include the use of unrelated or HLA-mismatched related donors, selective T-cell depletion of donor marrow, and the use of antithymocyte globulin or monoclonal anti-T-cell antibodies for the prophylaxis and treatment of acute graft-versus-host disease. Over the past few years, the administration of in vitro-generated EBV-specific cytotoxic T cells or anti-B-cell monoclonal antibodies has provided effective options for the prophylaxis or treatment of posttransplantation lymphoproliferative disease. Advances in quantitative polymerase chain reaction-based assays allow both the precise measurement of EBV load in peripheral blood samples and the identification of high-risk patients for early initiation of therapy. A major remaining challenge is to assess the significance of an elevated EBV load posttransplantation and to determine the indications for preemptive treatment.