The core symptoms of post-traumatic stress disorder (PTSD) include persistent reexperiencing of the traumatic event, avoidance of stimuli associated with the trauma, and autonomic hyperarousal. Many neurotransmitter systems and neurobiologic mechanisms may account for these primary symptoms of PTSD. Severe psychological trauma results in the parallel activation of these systems, producing an array of adaptive behavioral and physiologic responses necessary for survival. The pathophysiology of PTSD may involve dysfunction of several brain structures, particularly the amygdala, locus coeruleus, and hippocampus, as well as noradrenergic system and hypothalamic-pituitary-adrenal (HPA) axis. The neuroendocrinology of PTSD, and specifically hypothalamic-pituitary-adrenal axis alterations, are ways of examining biologic heterogeneity following trauma and its possible clinical implications. The decreased levels of cortisol, the increased responsiveness of glucocorticoid receptors, the increased sensitivity of the HPA negative feedback inhibition and its progressive sensitization are the neuroendocrine alterations specifically associated with the development of PTSD.