Iron is required for proper cell life functioning. Iron metabolism dysfunction leads in humans to deleterious situations. Maintenance of correct iron plasmatic bioavailability is crucial to permit adequate iron addressing to the different cell types. This implicates especially macrophages and enterocytes, ensuring the import of iron into plasma, as well as systemic signals, including hepcidin a peptide mainly produced by hepatocytes and secreted in plasma, which modulates iron leakage from these cells into plasma. The control of intracellular iron content is under the dependence of the IRE/IRP system which modulates cellular iron ingress and storage. The description of new iron metabolism genes, including hepcidin, paves the road for novel diagnostic tools and therapeutic strategies in the field of diseases associated with iron metabolism abnormalities.