Given the high rate of cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia (CML), logical future treatment strategies will include combinations of tyrosine kinase inhibitors and immunotherapies such as vaccines. Increased understanding of highly specific immune responses will lead to novel and improved immunotherapy strategies for CML patients. Such advances can be expected to revolutionize the field much in the same way that imatinib mesylate and other targeted small molecules have revolutionized our conception of traditional chemotherapy. This article begins with a brief discussion of why CML may represent a model disease for immunotherapy-based strategies. Laboratory evidence of the immunoresponsiveness of CML is discussed and used to highlight the principles for understanding tumor immunity. Finally,the authors discuss how advances in the understanding of the molecular and cellular nature of immunity are being translated into new therapeutic strategies for the treatment of CML.