Treatment with a chelating agent capable of sequestering iron and permitting its excretion from the body is the most widely-used therapeutic approach. Desferrioxamine was first introduced 30 years ago and is the only iron-chelating agent now in clinical use. A number of recent studies have shown that regular chelation therapy with desferrioxamine can prevent organ damage and improve survival in transfusion-dependent patients with thalassemia major and other disorders. However, desferrioxamine given orally is poorly absorbed and to be effective must be given by subcutaneous or intravenous infusion using a small portable syringe pump, ideally for 12 hours each day. Compliance with this regimen is frequently poor, particularly in adolescents with thalassemia major who may be at greatest risk for the lethal complications of iron overload. With modern transfusion programs, one of the main threats to life in patients with transfusion-dependent anemias is non-compliance with iron-chelation therapy. Moreover, the cost of desferrioxamine therapy in transfusion-dependent therapy exceeds $10,000 per year, in part because the drug must be isolated from bacterial cultures. Despite the limitations, trials of desferrioxamine have validated iron chelation as a therapeutic approach to iron overload.