Chronic myelogenous leukemia (CML) is the one of the most common chronic myeloproliferative disorders. It has become the paradigmatic disease for molecular diagnosis and monitoring for several reasons: (1) CML has a unitary molecular definition, requiring the demonstration of the t(9;22)(q34;q11) chromosomal translocation or its product, the BCR-ABL fusion gene; (2) The BCR-ABL chimeric protein is integral to CML leukemogenesis, as demonstrated in mouse transgenic leukemia models; (3) Blocking the BCR-ABL kinase, using the tyrosine kinase inhibitor (TKI) imatinib mesylate (Gleevec), results in regression of CML and durable clinical response in nearly all patients; (4) Daily lifetime therapy with imatinib (or similar second-generation TKIs) has become the standard therapy for CML, allowing standardized definitions of response and treatment resistance to be developed.