The association of cirrhosis with diabetes mellitus and bronze skin pigmentation was first recognized more than a century ago, when the term hemochromatosis (HC) was given to the condition. Hereditary hemochromatosis, also previously described as genetic or idiopathic hemochromatosis, is now known to result from an inborn error of iron metabolism leading to inappropriately increased iron absorption from the diet. The discovery of the hemochromatosis gene (HFE) and the observation that a single missense mutation, leading to a cysteine-to-tyrosine substitution at position 282 (Cys282Tyr or C282Y), is responsible for most cases of hereditary hemochromatosis have led to rapid advances in the field of iron metabolism. Although the basic defect is still not fully elucidated, much is known about the sequence of events leading to iron overload symptomatic disease, and rational effective therapy is available.