Chronic myeloid leukemia (CML), a hematopoietic stem cell cancer representing 15-20% of adult leukemias, is discussed. Epidemiology, staging biology, and monitoring techniques are reviewed.CML is a myeloproliferative disorder that affects all lineages of hematopoiesis. Final confirmation of CML comes with detection of the Philadelphia Chromosome (Ph) or BCR-ABL transcripts. The disease presents in one of three phases: chronic phase, accelerated phase, or blast crisis. Progression from chronic phase to accelerated phase usually involves the accumulation of additional cytogenetic aberrations and the arising of resistance to therapy. Although at one point mortality associated with CML was high, new kinase inhibitor therapies have markedly extended the life-span of these patients. These inhibitors were derived through the initial observation of the association of the Ph with CML and the eventual identification of the BCR-ABL oncogene which arises from this translocation. Analysis of the mechanism by which BCR-ABL transforms cells identified this protein as a tyrosine kinase and led to the targeting of this activity. The majority of patients present in chronic phase, which is where these kinase inhibitors have their greatest efficacy. Monitoring of disease progression is of critical importance as the prognosis drops significantly for patients with advanced disease. Blood counts, cytogenetics, and polymerase chain reaction (PCR) are currently used to assess disease. Blood counts are inexpensive but lack sensitivity. Cytogenetic karyotyping while requiring specialized training provides evidence of clonal evolution. Quantitative PCR is capable of tremendous sensitivity making it well suited for assessing response to therapy and the early detection of therapy failures.Our understanding of BCR-ABL has allowed the development of therapies, which may keep patients with CML in chronic phase indefinitely. This has created a situation in which patient monitoring is essential for detecting changes in the status of CML. The tests described here provide a comprehensive assessment of disease status allowing for effective patient management.