The introduction of recombinant human erythropoietin into clinical practice in the 1980 s was a major breakthrough in the treatment of the anemia of patients with CKD. The development of Erythropoietin Stimulating Agents (ESA’s) was aimed at replacing the insufficient endogenous erythropoietin (EPO) production related to CKD progression. In the early years, ESA administration was regarded by the nephrology community as a beneficial therapy for long-term dialysis patients whose Hb values fell to extremely low levels, making them transfusion-dependent. In addition, the reduction in the need for regular blood transfusions was another major benefit. Correction of iron deficiency with oral or intravenous iron supplementation can reduce the severity of anemia in patients with CKD and continues to be a cornerstone in the management of anemia till today. Iron supplementation is widely used in CKD patients to treat iron deficiency, prevent its development in ESA treated patients, raise Hb levels in the presence or absence of ESA treatment, and reduce ESA doses in patients receiving ESA treatment.