Our knowledge of iron homeostasis has grown enormously since the discovery of hepcidin at the turn of the century. Hepcidin was discovered as a liver-derived hormone that controls circulating iron levels by binding and degrading the iron exporter ferroportin in the gut and spleen, respective sites of iron absorption and recycling.  Until recently, the consensus was that iron levels within tissues were a function of circulating iron availability and controlled primarily at the point of uptake. Recent work from our laboratory has changed that consensus. We have discovered regulated iron export as an essential mechanism of local iron control in the heart, pulmonary vasculature, renal tubules and fetal liver1-5. These tissues produce their own hepcidin for cell-autonomous regulation of ferroportin-mediated iron export. Disruption of local this iron control in a manner that increases or decreases iron levels in these tissues is sufficient to impair their physiological function, even against a background of normal circulating iron levels. Importantly, we found that the pathways mediating the pathophysiological effects of disrupted local iron control differ from tissue to tissue, revealing new, unexpected and diverse functions for local iron control in systems physiology. These discoveries change our understanding of iron disorders from the simplistic notions of “too little” or “too much” iron, to that of sophisticated tissue-level iron control. They also highlight local iron-regulated pathways as new therapeutic targets in certain pathophysiologies. Our aim now is to translate these discoveries into better clinical management of iron disorders, particularly iron deficiency of chronic disease.