Chronic myeloid leukemia (CML) is characterized by the Philadelphia 
translocation that fuses BCR sequences from chromosome 22 upstream of the ABL 
gene on chromosome 9. The chimerical Bcr-Abl protein expressed by CML cells has 
constitutive tyrosine kinase activity, which is essential for the pathogenesis 
of the disease. Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl, has 
unprecedented efficacy for the treatment of CML. Most patients with early stage 
disease achieve durable complete hematological and complete cytogenetic 
remissions, with minimal toxicity. In contrast, responses are less stable in 
patients with advanced CML. This review highlights the pathogenesis of CML, its 
clinical features, and the development of imatinib as a specific molecularly 
targeted therapy. Aspects of disease monitoring and side effects are covered as 
well as resistance to imatinib and strategies to overcome resistance, such as 
alternative signal transduction inhibitors and drug combinations. Perspectives 
for further development are also discussed.