Infants are subjected to both endogenous and exogenous corticosteroids in the pre- and postnatal periods. Stress to the mother before birth, or to the child postpartum, can give rise to high, chronic endogenous corticosteroid levels caused by activation of the hypothalamic-pituitary-adrenal (HPA) axis. Physician-administered exogenous corticosteroids are also used in the management of a wide spectrum of pre- and postnatal conditions. The long-term effects of corticosteroids in developing humans are not well known. Studies in animals, however, indicate that both natural stress and exogenous corticosteroids can have long-lasting and deleterious effects on the body, brain, behavior, and hypothalamic-pituitary-adrenal axis of developing infants. These data suggest that exogenous corticosteroids should be administered with caution, after careful benefit/risk analyses, and that, as far as possible, the developing brain should be protected against the effects of pre- and postnatal stress.