Most patients seeking allogeneic bone marrow transplantation lack an HLA genotypically identical sibling and require an alternative donor. Alternate donor options include the patient (autologous bone marrow transplantation), an HLA-haploidentical partially mismatched related donor, an HLA-phenotypically matched or partially mismatched unrelated donor, and an HLA-similar cord blood stem cell donor. When an allogeneic approach is preferred the risk of graft failure, graft-versus-host disease, fatal infection, and delayed immunoreconstitution is significantly greater than expected with a matched sibling donor. This has not always translated into inferior disease-free survival, possibly due to lower relapse rates seen in some studies from a graft-versus-leukemia effect potentially enhanced by major histocompatibility complex disparity. The degree and type of mismatch differs between alternative donors with broad variation in donor availability. Improvements are emerging in the prevention and treatment of graft rejection, acute and chronic graft-versus-host disease, and infectious complications that should result in improved survival, particularly when transplantation is applied to patients earlier in the disease course. No clear preference among alternate donor options has been established. In centers with experience, the use of an alternative donor option is not experimental in nature. The risk and outcome must be weighed on an individual patient basis. This approach to treatment is indicated in selective cases when conventional therapy is expected to offer little or no hope for cure.