Studies of the molecular function of HFE, the protein defective in hereditary hemochromatosis, have provided important insights into the control of intestinal iron absorption. A recent study suggests that HFE controls the recycling rate of the transferrin receptor and thereby ultimately controls the iron status of the enterocyte. In hereditary hemochromatosis, a defect in HFE causes relative iron starvation in the enterocyte leading paradoxically to the development of an "anemic" enterocyte phenotype in the midst of bountiful body iron stores. Despite ever-increasing stores of body iron, the inappropriately low iron status of the hereditary hemochromatosis enterocyte continues to drive the hyper-absorption of dietary iron, eventually leading to iron overload.