The prevalence of diabetes is increasing worldwide and constitutes a major threat to global health. A number of novel type 2 diabetes susceptibility genes have been identified in recent genomewide association studies (GWA). Nevertheless only up to 10% of the risk of type 2 diabetes can be explained by these genes, placing the focus on non-genetic environmental factors. It is well recognized that an adverse intrauterine environment leads to a compensatory programming of fetal metabolism that may be beneficial for short-term survival, but can be detrimental in the long term. This phenomenon is particularly detrimental if the prenatal nutrient restriction is followed by a postnatal nutrient abundance, leading to rapid catch-up growth and increased risk of later development of obesity and type 2 diabetes, including the metabolic syndrome. Many defects present in patients with overt type 2 diabetes are detectable at the age around 20 years in lean and otherwise healthy young men born with a low birth weight, strongly suggestive of an important role of intrauterine programming in the etiology and pathophysiology of type 2 diabetes. In this review we will focus on the complicated physiological and molecular mechanisms as well as abnormalities of metabolism linking low birth weight (LBW) with an increased risk of type 2 diabetes several decades later in life.