There is now widespread agreement that small size at birth is associated with an increased risk of the metabolic syndrome (glucose intolerance, high blood pressure, and dyslipidemia) and related pathologies, including cardiovascular disease in later life. Evidence is emerging that suggests that programming of hormonal systems in response to an adverse fetal environment may be one of the mechanisms underlying these long-term consequences of growth restriction in early life. In particular, alterations in neuroendocrine responses to stress may be important. Recent research suggests that increased adrenocortical and sympatho-adrenal responses are associated with small size at birth. Epidemiological studies show that such physiological alterations in these neuroendocrine systems may have potent effects on risk of cardiovascular disease through their influence on risk factors, such as plasma glucose and lipid concentrations and blood pressure.