In pregnancy, glucocorticoids derived from the maternal system and acting via the placenta are essential for the maturation, development and survival of the fetus in all mammalian species. However, in utero exposure to maternal stress and excess glucocorticoids, either endogenous or synthetic, can be detrimental to fetal growth, development and survival. Pregnancy complications where the fetus is exposed to excess glucocorticoids or inflammation can increase the risk of fetal growth restriction and have long term consequences for the health of live offspring. The physiological mechanisms that confer different outcomes in morbidity and mortality of the fetus exposed to stressful environments may be driven by differences in the expression pattern of placental glucocorticoid receptor (GR) isoforms. Our team has identified the presence of multiple GR protein isoforms in the placenta of the human, guinea pig and the mouse that vary in relation to gestational age at delivery, sex, glucocorticoid exposure, fetal growth and maternal health. We propose that some GR isoform patterns are protective against an adverse outcome for the fetus while others may be detrimental to fetal growth and survival. We have recently discovered that in small for gestational age (SGA) pregnancies there is increased GRα-D1 expression in both the cytosolic and nuclear compartments of the placenta when compared to appropriate for gestational age pregnancies (AGA). These placentae also have GRα-A isoform expressed in both cellular compartments but increased expression of inflammatory genes that would normally be suppressed by the presence of GRα-A. These data suggest GRα-D1 may play a central role in activating proinflammatory mechanisms in the placenta and provides a mechanism for the dichotomy observed in SGA pregnancies where there are increased concentrations of glucocorticoids and high circulating levels of pro-inflammatory cytokines.