The essential role of parvocellular neuroendocrine cells (PNCs) in the paraventricular nucleus of the hypothalamus (PVN) is to translate real or perceived challenges into a comprehensive glucocorticoid (GC) hormone response. Synaptic inputs encoding physical and psychological stress engage the hypothalamic–pituitary–adrenal axis (HPA) by increasing PNC activity, and corticotropin-releasing hormone production and release. Following robust recruitment in response to stress, GCs feedback to dampen PNC responses. Here we review the contributions of glutamate and GABA synapses in PVN to the initiation and termination of the stress response. The reliability of HPA responses to a given stress can vary as a function of prior experience. Within this context, we examine possible synaptic correlates that allow this neuroendocrine system to learn and adapt following stress challenges.