There is now a substantial body of evidence that the immune system can help eradicate leukemia. While alloreactive T cells may play this role after allogeneic bone marrow transplants (BMT), T-cells may also exist which are able to recognize processed leukemia specific antigens such as mutant oncogenes/fusion proteins. In addition, a contribution may come from major histocompatibility complex unrestricted but leukemia-selective killing by natural killer/activated killer cells. These effector mechanisms may be augmented by administration of interleukin 2 after chemotherapy or autologous BMT. Finally, techniques of gene marking may help to determine more accurately the site and characteristics of minimal residual disease and thereby improve the targeting of immune mediated eradication of leukemia.