Myeloid forms of leukemia would seem to be an ideal disease for investigators wishing to develop targeted immunotherapy because the leukemia is derived from antigen-presenting cells and because clinical data have demonstrated that there is potent T-cell immunity to chronic myeloid leukemia when donor lymphocyte infusions are used to treat relapse after transplantation. However, clinical vaccine studies have had to wait for the identification of specific antigens, some of which have recently been identified, and for a more complete understanding of basic tumor immunology. Here we review relevant fundamental T-cell biology, the nature of some important leukemia-associated antigens, and the preliminary results from recent clinical vaccine trials for leukemia. Although these studies are still early, they offer evidence that effective immunity to leukemia is possible after vaccination, thus setting the stage for future combined therapies.