Iron deficiency is prevalent in patients with chronic kidney disease (CKD), and use of oral and intravenous iron in patients with CKD who do not require dialysis might obviate or delay the need for treatment with eythropoiesis-stimulating agents (ESAs). Patients on hemodialysis have lower intestinal iron absorption, greater iron losses, and require greater iron turnover to maintain the ESA-driven red cell mass than do healthy individuals. In these patients, intravenous iron reduces ESA dose requirements and increases the likelihood of maintaining levels of hemoglobin within the desired range. Oral iron is inferior to intravenous iron in patients on hemodialysis, in part because elevated serum levels of hepcidin prevent intestinal absorption of iron. Increased levels of hepcidin also impair the normal recycling of iron through the reticuloendothelial system. Levels of serum ferritin and transferrin saturation below 450 pmol/l and 20%, respectively are indicative of iron deficiency, but values above the normal range lack diagnostic value in patients with CKD on dialysis. The availability of various iron preparations and new developments in delivering iron should enable adequate provision of iron to patients with CKD. This Review examines the efficacy, safety and use of iron supplementation therapy for the treatment of anemia in patients with CKD.