Chronic iron overload corresponds to a variety of genetic and acquired diseases. Genetic iron overload encompasses HFE- and non-HFE-related hemochromatoses. Acquired iron overload is mainly due to multiple transfusions and to dyserythropoiesis. The damaging effect of iron excess concerns numerous organs and can therefore lead to miscellaneous clinical features, related especially to liver, heart, pancreas, and rheumatological complications. Those complications alter not only the quality of life but also life expectancy. The diagnostic approach has become essentially noninvasive. It rests—besides clinical examination—on serum iron parameters (especially ferritin and transferrin saturation), on iron-MRI, and, whenever indicated, on genetic testing. The treatment, in hepcidin deficiency-related iron overload, remains based on venesection therapy but should resort in the future to hepcidin supplementation. Transfusional iron overload has greatly benefited from the design of oral iron chelators.