Fetal growth restriction (FGR), reflective of an adverse intrauterine environment, confers a significantly increased risk of perinatal mortality and morbidity. In addition, low birthweight associates with adult diseases including hypertension, metabolic dysfunction and behavioural disorders. A key mechanism underlying FGR is exposure of the fetus to glucocorticoids which, while critical for fetal development, in excess can reduce fetal growth and permanently alter organ structure and function, predisposing to disease in later life. Fetal glucocorticoid exposure is regulated, at least in part, by the enzyme 11β‐hydroxysteroid dehydrogenase type 2 (11β‐HSD2), which catalyzes the intracellular inactivation of glucocorticoids. This enzyme is highly expressed within the placenta at the maternal‐fetal interface, limiting passage of glucocorticoids to the fetus. Expression of 11β‐HSD2 is also high in fetal tissues, particularly within the developing central nervous system. Down‐regulation or genetic deficiency of placental 11β‐HSD2 is associated with significant reductions in fetal growth and birth weight, and programmed outcomes in adulthood. To unravel the direct significance of 11β‐HSD2 for developmental programming, placental function, neurodevelopment and adult behaviour have been extensively investigated in a mouse knockout of 11β‐HSD2. This review highlights the evidence obtained from this mouse model for a critical role of feto‐placental 11β‐HSD2 in determining adverse programming outcomes. This article is protected by copyright. All rights reserved.