A growing body of literature supports the use of intravenous iron as a compliment to erythropoiesis stimulatory therapy and in a significant number of disease states where iron is necessary and oral iron is ineffective or not tolerated. The differences in efficacy, safety, and clinical nature of serious adverse events that occur with the various iron preparations are poorly understood. Misinterpretation of adverse events leads to underutilization of this important treatment modality. Understanding the history of the development and use of intravenous iron is crucial to appreciate its importance in the management of anemias of dialysis, cancer, and cancer chemotherapy and properly assess side effects and toxicity. The benefits seen with intravenous iron therapy are independent of the pretreatment levels of serum ferritin, iron, total iron binding capacity, and percent transferrin saturation. Intravenous iron has been shown to overcome hepcidin induced iron restricted erythropoiesis in iron-replete patients. Available clinical and experimental data suggest that increased utilization of intravenous iron should be considered.