From a global perspective, severe systemic iron overload occurs predominantly in individuals affected by geographically specific genetic mutations that permit the daily absorption from the diet of more iron than is physiologically needed. Two main types of hereditary iron overload are well recognized: (1) HLA-linked hemochromatosis in populations derived from Europe and (2) iron overload complicating thalassaemia major and intermedia syndromes in Southeast Asia, the Middle East, and the Mediterranean. Another very common form of iron overload occurs in Africa and is clearly related to high dietary iron content; recent evidence suggests that a genetic predisposition may also contribute to the pathogenesis. Patients with iron overload may develop multiorgan system toxicity; aggressive therapy with phlebotomy or iron chelation to remove excess iron from the body prevents organ damage and prolongs life.