Chronic myelogenous leukemia (CML) is a lethal disease of the hematopoietic stem cell. Bone marrow transplantation has highlighted the importance of allogeneic disparity in maintaining remissions in CML. However, it has been unclear whether the immune effect against CML is mediated by T cells, natural killer cells (NK) or a combination of both. We have previously demonstrated that autologous activated NK are capable of selectively lysing malignant CML progenitors while sparing benign progenitors. NK effectors may play an important role in CML since NK lytic function, clonogenic frequency and proliferative capacity decrease as CML progresses from chronic phase to advanced phase and blast crisis. Incubation of CML NK with IL-2 is capable of restoring cytolytic activity to normal levels. We hypothesize that activated NK represent a potential therapy against CML to maintain remissions in a minimal residual disease setting induced by autologous transplantation. Clinical trials are in progress to test whether IL-2 based immunotherapy and activated cell infusions play a therapeutic role in CML.