Bacterial infection is a significant cause of morbidity and mortality in hemodialysis patients, and a number of studies have implicated iron overload as a risk factor for bacterial infection in these patients. While the underlying cause of increased susceptibility to bacterial infection is not completely understood, evidence suggests that iron overload alters the chemotactic and phagocytic properties of neutrophils, thereby reducing their ability to kill invading pathogens. T-cell function also appears to be altered. In addition, high levels of serum iron may promote replication and dissemination of bacterial pathogens that use iron as a growth factor. With the introduction of recombinant human erythropoietin therapy for hemodialysis patients, the need for red blood cell transfusions has been reduced and iron overload occurs much less frequently. Several recent studies have indicated that iron overload, which is suspected in the presence of high serum ferritin levels, may no longer be a significant risk factor for infection in hemodialysis patients receiving erythropoietin therapy. Major risk factors for infection in these patients include history of bacterial infection, immunosuppressive therapy, and vascular access via catheters rather than by arteriovenous fistula. In addition, anemia has recently been linked to an increased incidence of bacterial infection, particularly in patients receiving erythropoietin therapy. Therefore, repletion of iron stores and maintenance of iron balance without iron overload may prove to be important factors in reducing the incidence of bacterial infections in hemodialysis patients. However, the relationships between iron levels, anemia, and susceptibility to bacterial infection require further investigation.