Disequilibrium of hormonal intercommunication between the maternal brain and the developing fetal–placental unit increases morbidity and mortality risk for the mother–baby dyad. As a novel yet temporary endocrine organ, the placenta serves as a physical and immunologic barrier that facilitates exchange of nutrients and elimination of fetal waste. Steroid and peptide-based hormones secreted by the placenta and other neuroendocrine organs induce adaptations in maternal physiology accommodating fetal growth and development and enabling lactation postpartum. Human placental growth hormone, a peptide hormone continuously secreted at increasing concentrations throughout pregnancy, is a primary determinant of maternal insulin resistance and gestational diabetes.