The emergence of new chelators is likely to have a major impact on the treatment of thalassemia major, sickle cell disease and other hematologic disorders for which regular red cell transfusions are required either to correct severe anemia or to prevent major complications of the underlying disease. In comparison with deferoxamine, which requires prolonged parenteral infusion to achieve negative iron balance, orally active chelators offer the promise of easier administration and better compliance. Moreover, the availability of more than one iron chelator opens up the possibility of combination therapy to target iron in specific organs and to enhance overall iron excretion. Long-term studies, employing new technologies to measure tissue iron, are required to determine whether the new chelators will be as safe and effective as deferoxamine in maintaining control of iron stores and preventing iron-induced cardiac disease, the major complication of transfusional iron overload.