Intravenous iron treatment in hemodialysis patients improves the response to recombinant human erythropoietin (rHuEPO) and facilitates achievement of targets for hemoglobin and hematocrit. Excessive treatment, however, could expose patients to risks related to iron overload and oxidative stress. Therefore international treatment guidelines generally recommend that intravenous iron be discontinued when serum ferritin is greater than 500-1000 ng/ml. In this article we explore the relevant issues that inform the decisions as to what levels of serum ferritin are used as the upper limit for treatment. We conclude that the current published literature is inadequate for developing evidence-based guidelines. Clinical judgment is critical to properly weigh the risks and benefits of intravenous iron treatment in the context of the individual patient.