Many patients who undergo hematopoietic cell transplantation (HCT) present with anemia and have received red blood cell transfusions before HCT. As a result, iron overload is frequent and appears to be particularly prominent in patients with myelodysplastic syndromes (MDS). There is evidence that peritransplant events contribute to further iron accumulation, although the mechanism that disrupts normal iron homeostasis remains to be determined. Recent studies suggest that iron overload, as determined by ferritin levels, a surrogate marker for iron, is a risk factor for increased non-relapse mortality after HCT. Iron overload is associated with an increased rate of infections, in particular with fungal organisms. Furthermore. anecdotal data suggest that increased hepatic iron may mimic the clinical picture of (chronic) graft-versus-host-disease (GVHD). Whether excess iron contributes to GVHD and whether iron depletion, be it by phlebotomy or chelation, reduces the posttransplantation complication rate and improves transplant outcome has yet to be determined.