The severity of liver disease and its presentation is thought to be influenced by many host factors. Prominent among these factors is the level of iron in the body. The liver plays an important role in coordinating the regulation of iron homeostasis and is involved in regulating the level of iron absorption in the duodenum and iron recycling by the macrophages. Iron homeostasis is disturbed by several metabolic and genetic disorders, including various forms of hereditary hemochromatosis. This review will focus on liver disease and how it is affected by disordered iron homeostasis, as observed in hereditary hemochromatosis and due to HFE mutations. The types of liver disease covered herein are chronic hepatitis C virus (HCV) infection, alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), end-stage liver disease, hepatocellular carcinoma (HCC) and porphyria cutanea tarda (PCT).