Hemochromatosis and iron overload comprise a group of common disorders. Their ascent from curiosities at necropsy in the nineteenth century to clinically important conditions in the twenty-first century has been a long and difficult one. Eighty years passed from Trousseau's description of hemochromatosis in 1855 to Sheldon's suggestion in 1935 that this disorder was possibly heritable. Thirty-nine years later, Saddi and Feingold reported that the common type of hemochromatosis was inherited as an autosomal recessive trait. In 1975, Simon and colleagues demonstrated linkage of hemochromatosis to the human leukocyte antigen (HLA) complex on the short arm of chromosome 6, especially HLA-A*03. In 1988, Edwards and colleagues reported their observations of 11,065 Utah blood donors and their families who were evaluated with iron phenotyping, liver biopsies, and HLA typing. This landmark study demonstrated that hemochromatosis in western European whites is common, heritable, and often undetected. In 1996, Feder and colleagues discovered a HLA-linked hemochromatosis gene, now known as HFE. Subsequent important discoveries include those of non-HFE types of hemochromatosis, and the central role of hepcidin in controlling iron absorption.

The discovery of HFE stimulated a renaissance of learning about iron biology and disease. Using diverse plant and animal models and in vitro systems, basic scientists have explored the genetics, molecular biology, and toxicology of iron absorption and metabolism. Clinician scientists have sought unusual cases in their clinical rosters, study of which has permitted greater understanding of the genetics and pathophysiology of iron overload.