Human epidemiological and experimental animal studies have shown that the pattern of intrauterine growth is an important determinant of adult physiology with impacts on health, disease risk and, ultimately, lifespan. In particular, low birth weight is associated with adult dysfunction and overt disease of the cardiovascular, metabolic and endocrine systems in human populations (1). In experimental animals, changes in adult physiological phenotype occur after intrauterine growth restriction induced by a range of sub-optimal environmental conditions such as maternal under- or over-nutrition, hypoxia overexposure to stress hormones and administration of alcohol, caffeine and nicotine (2). Even when birth weight is unaffected by these conditions, there can be abnormalities in the subsequent functioning of physiological systems that impair the responses to environmental challenges later in life. The maternal environment during pregnancy, therefore, has an important role in controlling the development of individual fetal tissues and organ systems with physiological consequences long after birth. This epigenetic regulation of development is determined, in part, by the placenta, the primary source of the nutrients and oxygen required for intrauterine growth (2). Growth of the placenta per se is impaired by many of the environmental conditions known to restrict fetal growth and program adverse physiological outcomes later in life. However, the placenta is not just a passive conduit for nutrients and oxygen. It also regulates the bioavailability of hormones with direct and indirect effects on fetal growth and can adapt its transport characteristics in response to environmental signals to help maintain fetal growth, even when its own growth is restricted. Recent studies in rodents have shown that placental phenotype in late gestation is affected by natural variations in litter size and by maternal restriction of calories and/or protein, dietary composition, particularly of fat and sugar, and by overexposure to toxins, such as alcohol and caffeine, and to natural and synthetic glucocorticoids. These adaptations in placental phenotype are both morphological and functional and involve changes in the placental imprintome, nutrient transporter abundance and the intracellular signalling pathways involved in growth and nutrient sensing. They may also vary with the sex of the offspring and with gestational age at the time of the insult. Particularly when the placenta is growth restricted, there is often an increase in the relative proportion of the labyrinthine zone responsible for nutrient uptake and a thinning of the barrier between the maternal and fetal circulations, both of which will improve transplacental transfer of nutrients and oxygen. Similarly, small placentae frequently have a greater abundance of glucose and System A amino acid transporters which increases transport of these nutrients to the fetus per gram placental mass. These changes lead to a shift in maternal resource allocation in favour of fetal growth, despite poor maternal nutrient availability in certain circumstances (3). Changes in placental transport phenotype induced by sub-optimal environmental conditions are often associated with altered expression of several imprinted genes known to regulate placental development such Igf2, H19, Grb10 and Phlda2. Indeed, deletion of these genes causes alterations in placental nutrient transport and, in some instances, abolishes the adaptive response of the placenta to environmental challenges like undernutrition. In addition, there are changes in placental expression of proteins in the PI3K, MAPK and mTOR signalling pathways in response to maternal under- and over-nutrition and to deletion of the Igf2P0 transcript which suggests that that these pathways have a central role in mediating the effects of nutrient availability on placental phenotype. Comparison of the different genetically and environmentally induced placental phenotypes has led to the concept that the placenta may respond to fetal demand signals for nutrients, particularly when there is a mismatch between the fetal drive for growth and the materno-placental ability to supply the required nutrients. Thus, the environmentally induced changes in placental phenotype are likely to reflect a combination of signals arising from the nutritional status of the mother and fetus and from the ensuing degree of feto-placental compromise. By altering the amount and relative proportions of specific nutrients supplied to the fetus, these changes in placental phenotype can program development long after the original insult with adverse physiological consequences later in life (2,3).