Abstract Erythrocytes require iron to perform their duty as oxygen carriers. Mammals have evolved a mechanism to maintain systemic iron within an optimal range that fosters erythroid development and function while satisfying other body iron needs. This chapter reviews erythroid iron uptake and utilization as well as systemic factors that influence iron availability. One of these factors is hepcidin, a circulating peptide hormone that maintains iron homeostasis. Elevated levels of hepcidin in the bloodstream effectively shut off iron absorption by disabling the iron exporter ferroportin. Conversely, low levels of circulating hepcidin allow ferroportin to export iron into the bloodstream. Aberrations in hepcidin expression or responsiveness to hepcidin result in disorders of iron deficiency and iron overload. It is clear that erythroid precursors communicate their iron needs to the liver to influence the production of hepcidin and thus the amount of iron available for use. However, the mechanism by which erythroid cells accomplish this remains unclear and is an area of active investigation.