Genetic variants for hemochromatosis have been identified in human fossils that are over 4000 years old in Northern Ireland. Iron overload can lead to life-threatening complications, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. In this review, the emphasis is on developments in the diagnosis and treatment of C282Y-linked hemochromatosis. There is a need for earlier diagnosis leading to earlier treatment to prevent morbidity and mortality.