One of the important components of successful anemia therapy in patients with end-stage renal disease (ESRD) treated with recombinant human erythropoietin is the maintenance of adequate available iron. To accomplish this task, iron status must be serially monitored and supplemental iron administered as required. Among nonuremic subjects, the body's iron supply is tightly conserved, and iron deficiency usually develops only when chronic blood loss occurs. In patients with ESRD, iron deficiency occurs more frequently, because of increased external losses of iron, decreased availability of the body's storage of iron, and perhaps a deficit in intestinal iron absorption. Detecting iron deficiency in these patients can be difficult because of the inaccuracy of available diagnostic tests. The goals of iron therapy in ESRD include the prevention of iron deficiency by chronically supplementing iron, and the prompt treatment of overt iron deficiency. Oral iron supplements are inexpensive and safe, but poor patient compliance and reduced intestinal absorption may limit their effectiveness. Intravenous iron supplements have a greater efficacy then oral iron, which must be weighed against the small risk of allergic reactions. We present strategies for using the various diagnostic tests and treatment modalities to effectively manage iron supply for predialysis, hemodialysis, and peritoneal dialysis patients.