Iron deficiency is common in patients with kidney disease and is one of the primary causes for decreased response to recombinant human erthropoietin (rHuEPO) therapy. Serum ferritin and percent tranferrin saturation are regarded as the preferred indirect measurements of iron status. The National Kidney Foundation-Kidney Disease Outcome Quality Initiative (K/DOQI) guidelines recommend levels openface>100 ng/ml and>20%, respectively. These tests, however, have practical limitations and lack sensitivity and specificity to identify “functional” iron deficiency, which can occur in the presence of normal or even increased iron stores. Newer methods of assessing iron status are becoming available, with reticulocyte hemoglobin content (CHr) showing the most promise at this time. K/DOQ1 guidelines recommend that adequacy of iron should be based on the amount of iron needed to sufficiently achieve target hemoglobin and hematocrit levels of 11–12 g/dL, or 33–36%. Studies have demonstrated for a majority of hemodialysis and some predialysis and peritoneal dialysis patients that intravenous iron therapy is necessary to improve response, thus reducing the amount of rHuEPO needed to achieve these goals. Though intravenous iron is generally regarded as safe and effective, caution should be taken in regard to acceptable amounts of supplementation and long-term effects with the potential risk of iron overload.