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Anemia is one of the earliest and most frequent complications of chronic kidney disease (CKD). Anemia is associated with poor quality of life, increased cardiovascular morbidities and mortalities, and accelerated progression of renal function decline. Although the pathogenesis of anemia in CKD is multifactorial, absolute or relative erythropoietin (EPO) deficiency is central to it. Iron deficiency is the second most important cause of anemia. EPO-stimulating agents and iron replacement had been central in the management of anemia of CKD. Newer information regarding the role of hypoxia-inducible factor (HIF) mediating EPO release has the potential to change the current management paradigm. Orally administered HIF inhibitors are shown to be safer and have similar efficacy compared to ESAs, and may become the mainstay of treatment of CKD anemia.