Early-life events, such as stress and undernutrition, have been shown to programme life-long susceptibility to diseases. Indeed, adverse early life experience increases susceptibility to hypertension, hyperglycaemia, insulin resistance, obesity (in combination termed the metabolic syndrome) and psychiatric disorders such as depression and schizophrenia. Furthermore, increased fetal exposure to the stress hormones, glucocorticoids, have been implicated in the aetiology of this programmed phenotype. Under normal circumstances, the developing fetus is protected from high maternal glucocorticoids by expression of the glucocorticoid metabolising enzyme, 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2), which is highly expressed in the placenta and the developing fetus. In our laboratory, we have investigated several rodent models of prenatal glucocorticoid programming: administration of dexamethasone which is not metabolised by 11ß-HSD2, inhibition of 11ß-HSD2 activity by carbenoxolone treatment and a mouse with genetic deficiency of 11ß-HSD2. Data from these models will be reviewed, covering the effects of early life treatments on birth weight, growth trajectories and adult metabolic and cardiovascular parameters, together with central effects on stress reactivity and mood in the adult offspring. The important role of the hypothalamo-pituitary adrenal activity in the offspring, together with modified regulation and expression of key candidate genes that may underpin these phenotypes will be discussed.