The treatment of chronic myeloid leukemia (CML) achieved a great leap forward with the development of imatinib, a BCR-ABL kinase inhibitor. Alterations in the chemical structure of the inhibitor have produced agents that are more potent in vitro. In these studies, two new second-generation BCR-ABL kinase inhibitors, nilotinib and dasatinib, are compared with imatinib; these new drugs produce more complete responses and do so faster than imatinib. Both also appear to reduce the rate of progression to accelerated-phase and blast-phase disease. Chronic myeloid leukemia (CML) in the chronic phase, a clonal myeloproliferative disorder, is caused by the constitutively active BCR-ABL tyrosine kinase resulting from the translocation that produces the Philadelphia (Ph) chromosome. 1 , 2 Imatinib (Gleevec, Novartis Pharmaceuticals), an inhibitor of the BCR-ABL kinase, is the standard first-line therapy for patients with chronic-phase CML. 3 – 6 Dasatinib (Sprycel, Bristol-Myers Squibb), a second-generation BCR-ABL kinase inhibitor, has been approved as a second-line treatment for patients with CML if imatinib therapy fails. 4 – 7 Dasatinib therapy induces a complete cytogenetic response in approximately 50% of patients who do not have a response to imatinib or cannot . . .