Compelling epidemiological evidence suggests that the early environment is an important determinant of later risk of disease. In particular, low birth weight has been associated with an increased risk of cardiovascular and metabolic disorders, including hypertension, Type 2 diabetes mellitus and ischemic heart disease, independent of classical adult lifestyle risk factors such as smoking, adult weight, social class, excess alcohol intake and sedentary lifestyle. These observations have led to a revolutionary concept of early life physiological programming. The molecular mechanisms that underlie this relationship remain unclear, but one major hypothesis implicates fetal overexposure to glucocorticoid stress hormones. This article will review evidence for this hypothesis.