The Ph chromosome, the abnormality characteristic of chronic myelogenous leukemia, was discovered in 1963. However, the events responsible for the pathogenesis and transformation to accelerated and blastic phases are still unknown at the molecular level and are subjects of ongoing research. The positive outcome in a subset of patients with interferon therapy and the potential for cure with bone marrow transplantation have evoked controversy regarding the best approach for different groups of patients according to prognostic characteristics. At the same time, new therapies with promising results are being developed, both in the setting of chemotherapy and biologic therapy and in bone marrow transplantation. Homoharringtonine chemotherapy, the use of matched unrelated donors for bone marrow transplantation, and new modalities of purging for autologous bone marrow transplantation are some examples. Sensitive molecular techniques that allow for the detection of small numbers of bcr-abl-positive hematopoietic cells may provide new means of assessing the results of current and future therapies.