Epidemiological studies have shown a link between poor fetal growth and increased risk of developing type 2 diabetes. These observations are highly reproducible in many populations worldwide although the mechanisms behind them remain elusive. The ‘Thrifty Phenotype Hypothesis’ was proposed to explain the underlying causes of these relationships. Animal models of poor intrauterine nutrition have been utilised to help to define the causal factors and identify the molecular mechanisms. Programmed changes in beta cell function and insulin action have been a common feature of animal models of poor intrauterine nutrition. Fundamental underlying mechanisms are starting to emerge, including changes in the epigenotype and mitochondrial function.