At birth, the total body iron content is approximately 75 mg/kg, twice that of an adult man in relation to weight. During the first 6 mo of life, total iron body content increases slightly and exclusive breastfeeding is sufficient to maintain an optimal iron balance. Thereafter, iron body content substantially increases and the infant becomes critically dependent on dietary iron, provided by complementary foods. Numerous factors may contribute to nutritional iron deficiency in infancy, the most important being low body iron content at birth, blood loss, high postnatal growth rate, and a low amount and/or bioavailability of dietary iron. We have documented that the prevalence of iron deficiency declined in Italy as iron nutrition improved and that early feeding on fresh cow's milk is the single most important determinant of iron deficiency in infancy. Healthy full-term infants should maintain optimal iron balance by consuming a good diet, which can be summarized as follows: breastfeeding should be continued exclusively for at least 5 mo and then together with complementary foods containing highly bioavailable iron; infants who are not breastfed or are partially breastfed should receive an iron-fortified formula, containing between 4.0 and 8.0 mg/L iron, from birth to 12 mo of age; fresh cow's milk should be avoided before 12 mo of age.