Both autologous and allogeneic transplantation have been used to treat and cure patients with acute leukemia. An important component of the cure mediated by allogeneic transplantation comes from a graft-versus-tumor effect of the graft. The immunotherapeutic effect can be used to treat patients whose conditions relapse after allogeneic transplantation using donor leukocyte infusions. Research conducted in the areas of histocompatibility and stem cell biology have expanded the potential cellular sources for allogeneic transplantation, including matched unrelated marrow donors, unrelated cord blood, and allogeneic peripheral blood stem cells. Molecular studies in patients with leukemia have refined the assessments of minimal residual disease following therapy, including for patients who have undergone transplantation, and may provide an opportunity for intervention prior to overt relapse. The results of allogeneic and autologous transplantation preparative regimens, including the use of targeted radioimmunotherapy and individualized pharmacokinetics, may improve the effectiveness and lessen the toxicity of the treatment.