Hepcidin is synthesized in the liver and plays a pivotal role in iron homeostasis. It inhibits intestinal iron absorption, recycling of iron from the reticuloendothelial system, and mobilization of iron from hepatic stores. Opposing factors modify hepcidin expression and its influence on other iron regulators. Inflammation and high iron burden upregulate hepcidin. Anemia and hypoxia can dramatically suppress hepcidin production. The relative influence of each of these modifiers in the clinical setting is being elucidated in murine models and humans. This program will cover iron homeostasis as it relates to human disease. An overview of iron homeostasis, including the roles of hepcidin, ferroportin, hemojuvelin, and DMT1 will be covered. The clinical consequences of hepcidin excess as it relates to anemia of inflammation in humans and a murine transgene model will be elucidated. Conversely, the devastating consequence of untreated iron overload in beta-thalassemia and its relation to hepcidin deficiency will be presented.