Chronic myeloid leukemia (CML) is a stem cell disease in which BCR/ABL plays an important role as oncoprotein and also as a molecular and immunogenic target. In fact, several molecular targeted drugs and immunotherapies have been developed for this disease. In the current article, several immunotherapeutic approaches in CML, including interferon-alpha and vaccination, are discussed along with results from clinical trials and the value of such immunotherapies in the imatinib-era.