The use of tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of chronic myeloid leukemia (CML). For patient with chronic phase CML, frontline treatment with imatinib leads to an estimated event-free survival and overall survival at 8 years of 81 and 85%, respectively. Second-generation TKIs (dasatinib and nilotinib) have shown improved early cytogenetic and molecular end points compared with imatinib in frontline randomized studies. Imatinib, dasatinib and nilotinib are all now approved for the frontline therapy. Overall treatment success is dependent in large part on treatment compliance, effective management of side effects of the therapy and close monitoring and achievement of cytogenetic and molecular milestones.