INF-alpha therapy has been a major development in the treatment of CML. Maturing experience has confirmed its ability to induce durable major cytogenetic remissions, which translate into durable long-term disease control, and change in the natural history of the disease. Future studies aimed at improving the percentage and quality of cytogenetic remissions by combining INF-alpha therapy with other chemotherapeutic agents and/or biologicals are needed. The goal would be to identify strategies that can consistently achieve a major cytogenetic response rate of 40% to 50% in the general community setting with acceptable morbidity. Continued studies of the interactions between INF -alpha therapy and transplant strategies will permit the optimization of treatment for each individual patient with CML.