There is strong evidence that the endometrial glands play a key role in regulating placental development in many domestic species, but their contribution in the human has largely been ignored once implantation is complete. Here we re-evaluate their role during the first trimester. Connections between the glands and the intervillous space have been observed from day 17 post-conception through to the end of the first trimester. In the absence of a maternal arterial supply to the early placenta it is believed that the carbohydrate- and lipid-rich secretions represent an important source of nutrients during the first trimester, and possibly the beginning of the second trimester. The secretions also contain a variety of growth factors that may regulate placental morphogenesis since their receptors are present on villous and extravillous trophoblast, and villous endothelial cells. Other components of the secretions may modulate immune responses and trophoblast invasion at the materno-fetal interface. We speculate that lactogenic hormones secreted by decidual cells and the syncytiotrophoblast may act in concert with human chorionic gonadotropin to stimulate the secretory activity of glandular epithelial cells during the first trimester. There is circumstantial evidence, but as yet no conclusive proof, that deficient glandular activity is associated with pregnancy failure in the human.