This article begins with a review of the natural history of chronic myelogenous leukemia (CML), with an emphasis on prognostic features. Current standard therapy of CML with interferon-alpha based regimens, and interferon-alpha, in the context of allogenic stem cell transplantation is then discussed. Finally, some potentially effective novel agents including homoharringtonine, decitabine, ATRA, and topotecan are described.