Intensive iron therapy is now a generally accepted adjunct for the treatment of renal anemia with recombinant human erythropoietin. However, with the emerging role of iron in cardiovascular disease, carcinogenesis, infectious diseases, and other disorders, it is no longer appropriate to assume that any amount of stored iron is safe until proven otherwise. In this article, the history and current status of the "iron hypothesis" on ischemic heart disease are briefly reviewed, followed by comments on iron management practices for renal patients.