The graft-versus-leukemia effect following allogeneic stem cell transplantation (SCT) reduces the incidence of leukemic relapse and establishes that effector cells can eliminate or at least contain resistant leukemic stem cells. Natural killer cells also appear to play a role in directly lowering the rate of relapse following allogeneic SCT in patients with acute myeloid leukemia. To date, however, effective prevention of leukemic relapse by autologous immune effector cells has not been demonstrated. This article examines some of the challenges that limit autologous antileukemia immunity as well as some possible immunotherapeutic approaches that may help control leukemic relapse following autologous SCT.