Chronic myelogenous leukemia (CML) is a chronic myeloproliferative disorder with an uncontrolled production of maturing neutrophils being the predominant laboratory feature. The presence of translocation t(9;22), the so-called Philadelphia chromosome, is commonly acknowledged as the disease initiating event, and as such, is essential for the diagnosis of CML. This chapter addresses the pathophysiology of CML, explains diagnostic procedures, summarizes current treatment options including clinical results with imatinib in the treatment of CML, reviews current recommendations for monitoring and management of treatment failure, surveys results with approved second generation Abl kinase inhibitors after imatinib failure, and finally gives an outlook for promising treatment strategies examined in current and future clinical trials.