Epidemiological observations of associations between early life nutrition and long-term disease risk have prompted detailed experimental investigation of the biological basis of programming. Studies using rodent or large animal models have clearly established the biological plausibility of nutritional programming and are now yielding important information on underlying mechanisms. Nutritional interventions in pregnancy, including global food restriction, protein restriction, micronutrient restriction and excess fat feeding, determine a consistent cluster of disorders in the resulting offspring. The common association of such diverse nutritional disturbances with hypertension, glucose intolerance and adiposity suggests that a small number of simple common mechanisms are active in response to fetal nutrient imbalance. Studies of rodent models indicate that fetal undernutrition determines adult adiposity. It is unclear whether the increase in central adiposity is related to increased food intake or reduced energy expenditure, although evidence exists to suggest that both may act together. Rats subject to intrauterine protein restriction exhibit increased preference for high fat foods. Feeding of energy dense foods to rats that were undernourished in utero promotes a greater degree of obesity than is noted in animals subject to adequate nutrition in fetal life. There is evidence to suggest that programming of appetite may stem from remodelling of hypothalamic structures that control feeding and programming of the expression of genes involved in responses to orexogenic hormones. The early life programming of appetite and obesity is a complex phenomenon and our understanding of how maternal nutrition determines later energy balance is at a very early stage.