The introduction of the tyrosine kinase inhibitor (TKI) imatinib (Gleevec) into clinical practice resulted in a very dramatic prolongation of survival for most, but not all, patients with chronic myeloid leukemia in chronic phase (CML-CP). A leukemia with a median survival of about 5 years was transformed into one for which the survival in many cases promises to be comparable to that of normal persons of similar age. The more recently available TKIs, namely nilotinib (Tasigna) and dasatinib (Sprycel), produce more rapid responses but have not yet shown any overall survival advantage compared with long-term administration of imatinib. They are, however, useful in treating imatinib intolerance or resistance. There are currently two choices for initial treatment of CML-CP: (1) starting all new patients on imatinib and changing to a second-generation TKI in those who fail or who are predicted to fare badly, or (2) starting all new patients on a second-generation TKI. This choice may be based primarily on considerations of cost or possible side effects.