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For three decades, deferoxamine has been the only approved iron chelator. This drug has an extremely short-half life and is not orally absorbed; thus, a search has been ongoing for alternative chelators with less onerous delivery. Recently, several oral iron chelators and variations of deferoxamine to prolong the half-life have been developed. These and the methods of monitoring iron overload are the subjects of this review.New chelators, combinations of chelators and regimens for known chelators and their safety and efficacy are being studied in important preclinical and clinical trials.The care and clinical outcomes of patients with thalassemia and other iron-overload disorders may be markedly improved by recent discoveries and novel approaches to chelation therapy.