Chronic myeloid leukemia (CML) is a stem cell disease characterized by the BCR/ABL oncoprotein. The ABL kinase inhibitor imatinib is effective in most patients and considered standard first-line therapy. However, not all patients show a long-lasting response to this drug. In fact, resistance against imatinib has been described and is an emerging clinical problem in CML. For these patients, novel multi-kinase inhibitors such as nilotinib or dasatinib as well as stem cell transplantation, represent alternative treatment options. The decision concerning second-line therapies and selection of drugs is usually based on the presence and type of BCR/ABL mutations, the phase of disease, other disease-related factors as well as patient-related factors including age, co-morbidity, and pharmacologic determinants. The current article provides an overview on diagnostic and therapeutic strategies for patients with treatment-naïve and imatinib-resistant CML, together with proposed algorithms that were discussed and approved by members of the CML platform of the Austrian Society for Hematology and Oncology (OGHO) in 2007 and 2008. The resulting recommendations should assist in diagnosis and prognostication in CML, follow-up and disease-monitoring, patient selection for interventional therapies, and in the preparation and conduct of clinical trials.