Although dramatically effective for relapsed chronic myelogenous leukemia (CML), successful donor leukocyte infusion (DLI) remains limited primarily by inadequate responses for patients with diseases other than CML and by toxicity related to graft-versus-host disease (GVHD). Acute GVHD grades 2 to 4 follows 34% to 47% of infusions and chronic GVHD occurs in 33% to 61% of cases. Strategies to reduce the incidence and severity of GVHD while preserving the graft-versus-leukemia (GVL) effect, such as low-dose DLI, depletion of GVHD effector cells, and tumor-specific DLI, are reviewed.