Patients with hematologic malignancies in relapse after allogeneic bone marrow transplantation can be treated by infusing leukocytes from the original stem cell donor. The published literature on donor lymphocyte infusion (DLI) was reviewed. DLI induces complete remissions in the majority of patients with chronic myeloid leukemia (CML) in early-stage relapse and in less than 30% of patients with relapsed acute leukemia, myelodysplasia, and multiple myeloma. DLI-induced remissions of chronic phase CML are durable, but as many as half of patients with other diseases ultimately relapse. Complications of DLI include acute and chronic graft-vs-host disease (GVHD) and aplasia, which induce profound immunosuppression and susceptibility to opportunistic infections. There is a strong correlation of GVHD and disease response. Novel methods of augmenting the antitumor efficacy of DLI and of dissociating the graft-vs-leukemia effect from GVHD are needed. These studies will require an improved understanding of the cellular and molecular mechanisms of alloreactivity and the development of novel agents to control the nature and intensity of the alloimmune response.