Iron is an essential element mainly stored in the bone marrow and liver. Hemochromatosis is a condition caused by excessive iron deposition in various organ systems, including the liver, lungs, kidneys, the heart, the pancreas, joints, skin, and endocrine glands, leading to a wide spectrum of tissue damage and clinical presentations. Primary hemochromatosis, also known as hereditary hemochromatosis, usually results from a genetic mutation in genes, such as HFE, BMP2, HJV, HAMP, TFR2, and SLC40A1, involved in iron absorption, storage, and transport. Secondary iron overload is more prevalent with diverse etiologies including hematologic disorders, such as ineffective erythropoiesis and iron-loading anemias, frequent transfusion, and chronic liver diseases. The liver is the main target organ for hemochromatosis. Multiple modalities have been developed to evaluate hepatic iron overload, including iron staining, iron quantification on dry liver tissue, magnetic resonance imaging iron quantification, and mass spectrometry. Accurate diagnosis of hepatic iron overload requires an integrative evaluation of clinical history, iron metabolism studies, tissue examination for iron deposition, and necessary genetic counseling with appropriate genetic testing.