Meeting the iron requirements of infants and children is difficult, and supplementation or fortification of food with iron is often recommended. Although iron supplementation of infants and children with iron deficiency and iron-deficiency anemia may be beneficial, recent studies suggest that this may not be the case for those with adequate iron status, and adverse effects have been noted. The recent discoveries of proteins and peptides regulating iron absorption have enhanced our knowledge of iron metabolism in infants and children. Iron is taken up in the small intestine by divalent metal transporter-1 and is either stored by ferritin inside the mucosal cell or transported to the systemic circulation by ferroportin, while being oxidized by hephaestin to be incorporated into transferrin. Hepcidin, a small peptide synthesized by the liver, can sense iron stores and regulates iron transport by inhibition of ferroportin. However, regulation of iron transporters is immature in infants, possibly explaining the adverse effects of iron supplementation. Interactions among iron, vitamin A, zinc, and copper need to be considered when evaluating the effects of iron supplementation on infants and children.