Conventional myeloablative allogeneic hematopoietic cell transplantation produces considerable morbidity and mortality. These generally limit this treatment to patients in good medical condition who are younger than 55 years of age. T-cell-mediated graft-versus-tumor effects play a key role in the elimination of malignancy after allografting. Several investigators have sought to reduce regimen-related toxicities while optimizing graft-versus-tumor effects. Strategies can be broadly classified as (1) reduced-intensity regimens that retain some toxicity, and (2) minimally myelosuppressive regimens that rely on immunosuppression for allogeneic engraftment and resultant graft-versus-tumor effects. Although follow-up has been short, preliminary results are encouraging. Current challenges include defining a regimen that will facilitate full donor engraftment while minimizing toxicities and graft-versus-host disease. If long-term efficacy is demonstrated, such strategies will expand the options for patients who would not qualify for conventional allogeneic transplants.