The advent of nonmyeloablative preparative regimens and the expected lower regimen-related toxicities associated with them hold significant promise for extension of the use of allogeneic hematopoietic stem cell transplantation. Nonmyeloablative hematopoietic stem cell transplantation using human leukocyte antigen matched sibling donor, which carries a relatively low risk of transplant-related complications and can result in impressive antitumor responses, may benefit older patients and patients with preexisting organ impairment. However, more than 65% of patients in need of this procedure lack a human leukocyte antigen matched sibling donor. Therefore, attention has focused on alternative donors such as genotypically matched unrelated donors and partially mismatched related donors. Early clinical results suggest that the use of alternative donors is feasible, therefore potentially allowing full extension of the benefits of allografting to the group of patients in highest need.