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Overexposure of the developing fetus to glucocorticoids is a key mechanism linking early development with later life disease. In humans low birthweight, a marker of an adverse in utero environment, associates with increased fasting cortisol, increased hypothalamic-pituitary-adrenal (HPA) axis reactivity and with cardiovascular risk factors, cardiovascular disease and poorer cognitive function. Animal models suggest the HPA axis of female offspring is more susceptible to programming insults. We hypothesised that there would be similar sex differences in humans. We carried out a systematic review, searching Embase, Medline and Web of Science up to June 2014. Two independent researchers screenedarticles for eligibility. The29 includedstudies investigated the consequences of maternal stressors of asthma, psychosocial stress and glucocorticoid medications on HPA axis outcomes of placental glucocorticoid biology, and HPA axis function in earlyand later-life. Overall, the studies reported sex differences such that female offspring were more responsive to stress both in earlyand later-life: females had lower birthweight, increased therapeutic responsiveness to glucocorticoids, increased diurnal cortisol secretion and HPA axis reactivity, compared to males. Further, in comparison to males, the female placenta increased its permeability to maternal glucocorticoids following maternal stress with downregulation of the enzyme 11-beta-hydroxysteroid dehydrogenase (which converts active cortisol to inactive cortisone) in response to maternal glucocorticoid exposure or maternal asthma. Theobservationsof increasedprogrammedvulnerabilityof theHPA axis in females is consistentwith data fromanimalmodels andmay be a mechanism underlying sex differences in later life diseases including depression and cardiometabolic disease.