The concept of developmental programming of future health has had a galvanizing impact on thinking, both by those concerned with the aetiology of disease in adult life and its impact on future global human health, and by those interested in developmental biological mechanisms. There is strong evidence of long-term programming taking place in the neonatal period in the marked inverse relationship between neonatal microbial exposure and later airways hyper-reactivity. There is extensive evidence that normally grown substantially preterm fetuses have a life course very different from their intrauterine contemporaries; thus they are programmed differently following early expulsion from the uterus. The roots of the developmental programming paradigm lie in medical epidemiology and in the impact of earlier environmental experiences. Programming provides ever more challenging questions, and some of the answers are beginning to emerge with regard to establishing the role of the placenta in this critical process.