In this paper the authors review the literature on biological and treatment studies of post‐traumatic stress disorder (PTSD) and present current unifying hypotheses regarding the pathophysiology. The psychophysiological studies stress overarousal, while endocrine studies suggest a decreased Cortisol production in denial and low symptom states with increases in highly symptomatic states. Suggestive evidence is provided that PTSD is associated with permanent changes in brain mechanisms involving the locus coeruleus, amygdala, and the hypothalamo‐pituitary‐adrenal axis. Drug treatments are promising but not fully satisfactory as yet. Directions for further research are provided.