The vast majority of erythropoietin (EPO)-treated peritoneal dialysis (PD) patients require iron supplementation. Most authors and clinical practice guidelines recommend primary oral iron supplementation in PD patients because it is more practical and less expensive. However, numerous studies have clearly demonstrated that oral iron therapy is unable to maintain EPO-treated PD patients in positive iron balance. Once patients become iron-deficient, intravenous iron administration has been found to more effectively augment iron stores and hematologic response than does oral therapy. We recently performed a prospective, cross-over trial in 28 iron-replete PD patients and showed that twice-monthly outpatient iron polymaltose infusions (200 mg) were a practical and safe alternative to oral iron. That treatment produced significant increases in hemoglobin concentration and body iron stores. The additional expense of intravenous iron therapy was completely offset by reductions in EPO dosage. Careful monitoring of iron stores is important in patients receiving intravenous iron supplementation in view of epidemiologic links with infection and cardiovascular disease. Nevertheless, a growing body of evidence suggests that, as has been found for hemodialysis patients, intravenous iron therapy is superior to oral iron supplementation in EPO-treated PD patients.