Chronic iron overload from frequent blood transfusions to treat patients with severe anemias leads to significant morbidity and mortality. Although desferrioxamine, the current standard of care, is an effective iron chelator with long-term evidence, it requires tedious subcutaneous infusion that reflects negatively on patient compliance. Deferiprone opened the horizon for an era of oral iron chelators. Although collective evidence proved its efficacy, safety issues are still of high concern and require regular monitoring. The experience with these two drugs helps better delineate the optimal goals of iron chelation therapy and the ideal iron chelator.