Abstract
Imatinib mesylate has revolutionized the treatment landscape for patients with newly diagnosed chronic myeloid leukemia. Follow-up has shown excellent response rates, progression-free survival, and overall survival after 8 years. However, some patients develop resistance to imatinib treatment because of a multitude of reasons. Strategies to overcome resistance include dose escalation of imatinib or switching to a second-generation tyrosine kinase inhibitor or to one of the newer non-tyrosine kinase inhibitors. This article guides the treating physician with a rational approach in the management of patients with chronic myeloid leukemia who fail initial treatment with imatinib or lose response while on therapy with imatinib.