Dysregulation of metabolism and utilization of iron can lead to the development and maintenance of anemia of CKD. Anemia is prevalent among patients with CKD. The markers of iron sufficiency or availability of iron are far from perfect which results in inaccurate diagnosis and treatment of anemia with poor outcomes. Hepcidin, a 25 amino acid peptide produced by the hepatocytes, has emerged as the key regulator of uptake and release of iron in the tissues to maintain a steady supply of iron to erythron and other tissues while avoiding higher levels of iron that could be detrimental to the organs. Hepcidin itself is regulated by the supply of iron, the need for erythropoiesis, and the state of inflammation. Alterations in hepcidin levels are associated with restricted erythropoiesis, anemia, and iron overload. Discovery of hepcidin and elucidation of its mechanism of action and consequences of its upregulation and suppression have unraveled important insight into many hematologic disorders including anemia of CKD. This knowledge has also unlocked unique opportunities to modulate hepcidin via agonists and antagonists of hepcidin and its feedback pathways to treat clinical conditions. Many such agents are being developed and have potential therapeutic utility in future.