The recent introduction of imatinib mesylate has deeply changed the treatment of chronic myeloid leukemia. This first physiopathology-based therapy, which targets the molecular anomaly that gives rise to the disease (the abnormal tyrosine kinase activity generated by the fusion protein P210 Bcr-Abl) has demonstrated an impressive activity. However, its long-term efficacy remains unknown. On the other hand, other treatment modalities, such as stem cell transplantation or experimental ones (immunotherapy) are also profoundly evolving. In this review, the authors have tried to synthesize the current knowledge of this disease and suggest a therapeutic strategy based on the currently available data.