During pregnancy, the maternal brain drives a series of adaptive mechanisms that are fundamental for allowing fetal growth and development, protecting both mother and fetus from adverse programming and timing of parturition. This neuroendocrine concept is even more complex as fetal brain and placenta also participate as regulators of maternal-placental-fetal physiology. The placenta is now seen as a neuroendocrine organ, acting as a source of several neuroactive factors that may exert their biologic effects either locally or by entering maternal and fetal circulation, thus acting in an autocrine, paracrine, and endocrine manner. A variety of hypothalamic neurohormones (GnRH, GHRH, somatostatin, CRH, oxytocin) are expressed in the placenta. When stress occurs during pregnancy, the maternal, fetal, and placental hypothalamic-pituitary-adrenal (HPA) axes are activated to stimulate a series of responses contributing to maintain physiologic conditions while at the same time avoiding the adverse effects of stress on the mother and offspring. However, when stress is excessive, a number of obstetric complications may occur, such as preterm birth, pre-eclampsia and intrauterine growth restriction, related to an impairment of the placental adaptive response.