Wilson disease (WD) and high FE (HFE)-associated hemochromatosis are autosomal-recessively inherited metabolic diseases of the liver. Copper overload in the case of Wilson disease and iron overload in the case of hemochromatosis lead to organ damage of the liver and other organs. The diagnosis of Wilson disease is often delayed, as the clinical picture is wide, and not a single test per se is diagnostically specific. Medical therapy should be started as soon as a diagnosis is established and should be continued lifelong. In contrast to Wilson disease, the diagnosis of HFE-associated hemochromatosis is straightforward. Hemochromatosis can be diagnosed based on elevated ferritin and transferrin saturation levels, in combination with a homozygous HFE C282Y mutation. After diagnosis, treatment with phlebotomies in order to remove excess iron can be initiated and is typically well-tolerated. When treated, both diseases, Wilson disease and hemochromatosis, have a very good prognosis, with typically at least partial regression of liver damage and symptoms.