Chronic myelogenous leukemia (CML) was the first human malignancy where a consistent chromosomal abnormality, the BCR-ABL translocation, was identified as the causative genetic aberration. There is a mounting body of evidence suggesting that CML cells are particularly good targets for immunological surveillance mechanisms, the most intriguing being the curative effect of allogeneic donor lymphocyte infusion given in relapsed disease after allogeneic bone marrow transplantation. Likewise, interferon alpha (IFN alpha), which has long been considered as the standard conservative therapy in CML, may exert its life-prolonging effect by activating immunological effector functions. This review will focus on the recent advances in the understanding of the contribution of IFN alpha in eliciting T-cell responses against self-antigens in CML.