Environmental effects on the materno-foetal interaction determine birth outcomes that predict health over the lifespan. Thus, maternal undernutrition or stress associate with low birth weight, leading to an increased risk of metabolic and cardiovascular illness in the offspring. We argue that these effects are, in part, mediated by direct and indirect effects on the hypothalamic-pituitary-adrenal (HPA) axis such that (i) the effect of maternal adversity on foetal growth is mediated by adrenal glucocorticoids and (ii) environmental adversity alters maternal physiology and behaviour, which then programs HPA activity in the offspring.