The myeloablative doses of chemotherapy and radiation used with conventional allogeneic hematopoietic cell transplantation produce considerable morbidity and mortality that generally limit this treatment to patients younger than 55 years of age and in good general medical condition. It has become clear that T-cell-mediated graft-versus-tumor effects play an important role in the elimination of malignant disease after allotransplants. Several investigators have sought to reduce regimen-related toxicities while optimizing graft-versus-tumor effects. Strategies can be broadly categorized as reduced-intensity regimens that retain some toxicities and require hospitalization, and minimally myelosuppressive regimens that rely on immunosuppression for allogeneic engraftment and resultant graft-versus-tumor effects. The latter approach can be performed in the ambulatory care setting. Preliminary results are encouraging. If long-term efficacy is demonstrated, such strategies would expand treatment options for patients who would otherwise be excluded from receiving conventional allografts.