Advances in the treatment of iron overload hold the promise of making long-term transfusion therapy a safer approach to the management of thalassemia major, sickle cell disease, and numerous other hematologic disorders. The responsibility now placed on the treating physician is to monitor iron stores carefully, to begin chelation therapy at an appropriate time, and to encourage regular use of deferoxamine. For the clinical investigator, the success of chelation therapy with deferoxamine should prompt an intensive search for new chelators. These new chelators should be not only effective but also inexpensive, readily available, safe, and easy to administer.