The neuroendocrine system in pregnancy involves highly complex maternal, fetal, and placental mechanisms, which are critical for the maintenance of pregnancy, the timing of parturition, fetal growth, and protection from adverse fetal programming. The brain and placenta are both central organs in the responses to stress, and the maternal, fetal, and placental hypothalamus-pituitary-adrenal (HPA) axes play a significant role in controlling some of the adaptive mechanisms during pregnancy. The secretion of maternal and fetal HPA axis hormones increases throughout pregnancy. Corticotropin-releasing hormone (CRH) represents the main regulator of the axis as, when released from the hypothalamus, it stimulates adrenocorticotropic hormone (ACTH) release from the anterior pituitary and consequently cortisol secretion from the adrenal cortex. However, the major source of maternal circulating CRH in human pregnancy is the placenta. Indeed, the placenta, may be considered a neuroendocrine organ rich in neurohormones, neuropeptides, and neurosteroids. Stress-related hormones, such as CRH, urocortins, oxytocin, and prolactin, are key placental neuroendocrine factors mediating both endocrine (metabolism, immune function, cardiovascular changes) and paracrine (uterine contractility, local hormone production) mechanisms involved in term and pre-term birth. Aberrations in neurohormones secretion, as an adaptive response of the feto-placental unit to adverse environmental conditions, may contribute to the development of gestational disorders, such as hypertensive disorders of pregnancy, intrauterine growth restriction, and gestational diabetes.