It is now well established that the efficacy of allogeneic hematopoietic stem cell transplant for eradicating a variety of hematologic malignancies is related to antitumor activity mediated by donor immune cells contained in the stem cell graft. Recent studies have provided fundamental insights into the nature of the effector cells and target molecules that are responsible for the graft versus tumor effect. T cells specific for minor histocompatibility antigens can mediate potent antitumor activity but are also responsible for graft versus host disease (GVHD). The molecular characterization of minor antigens has suggested ways of potentially separating antitumor activity from GVHD. The challenge for the future is to continue to build on our understanding of the allogeneic graft versus tumor effect and develop strategies that can be incorporated into clinical practice to augment this effect without GVHD.