Epidemiological studies demonstrated a clear phenomenological association between low birth weight and increased cardiometabolic risk later in life, very similar to that in high birth weight subjects. Pre- and/or neonatal overfeeding appears to be an etiological clue. In animal studies, irrespective of birth weight neonatal over-nutrition leads to later overweight, impaired glucose tolerance and cardiometabolic alterations. Probably, perinatally acquired alterations of DNA methylation patterns of gene promoters of central nervous regulators of body weight and metabolism play a key role in mediating these relationships. In humans, the long-term impact of neonatal nutrition is conclusively demonstrated by studies on the consequences of breastfeeding vs. formula-feeding. Taken together, the quantity and quality of nutrition during neonatal life plays a critical role, beyond prenatal development, in the long-term programming of health and disease. This opens a variety of opportunities and challenges to primarily prevent chronic diseases, e.g. the metabolic syndrome. (C) 2012 Elsevier Ltd. All rights reserved.