Epidemiological studies have revealed strong inverse relationships between birthweight and the risk of developing type 2 diabetes mellitus (T2DM) and the metabolic syndrome. The mechanistic basis of these relationships remains the subject of research and debate. Evidence for the importance of the fetal environment has been obtained from both human and rodent studies. Studies of monozygotic twins have shown that genetic effects cannot explain these relationships entirely, if at all. Fetal and early postnatal growth restriction produced by feeding a reduced protein diet to rat dams leads to T2DM in old male offspring and, if combined with an obesity-inducing diet after weaning, to all the features of the metabolic syndrome.