Hepcidin (hepatic bactericidal protein) was initially identified as a urinary antimicrobial peptide rich in cysteine. Further studies showed that hepcidin is overexpressed with iron overload and that it plays a significant role in iron homeostasis in knockout animals with iron storage disease. The complete abrogation of hepcidin entails excessive intestinal absorption of iron and increased iron release by macrophages, a condition that leads to iron overload. Hepcidin performs its different functions via a single biochemical mechanism: hepcidin-ferroportin interaction. Intestinal epithelial cells and reticuloendothelial macrophages use the same transporter, ferroportin, to transport iron in the plasma. Moreover, macrophages and enterocytes exhibit strong upregulated ferroportin expression in the erythropoietic response in an iron-restricted state. Specific methods were recently developed to measure hepcidin and evaluate its diagnostic potential. The competitive ELISA test uses biotinylated or radioiodinated hepcidin as a tracer. However, mass spectrometry is used for the hepcidin assay; this involves standards labeled with hepcidin isotopically or standards that bind the hepcidin-truncated molecule. Understanding the physiological processes of hepcidin has made it possible to redefine the pathogenetic mechanisms of anemia. There are several physiopathological mechanisms potentially involved in the genesis of anemia associated with heart failure. These include hemodilution, anemia of chronic disease, decreased renal blood flow and iron deficiency. It has also been recognized that iron metabolism may be governed by mechanisms beyond absolute iron store quantities. Hepcidin production can be induced by inflammation, which explains the reduced availability of iron in anemia of chronic disease, whereas anemia and hypoxia have been shown to increase iron absorption and mobilization by decreasing hepcidin production.