Exposure to a traumatic event is required for the diagnosis of posttraumatic stress disorder (PTSD). The symptoms of PTSD are believed to reflect stress-induced changes in neurobiological systems and/or an inadequate adaptation of neurobiological systems to exposure to severe stressors. More recently, there have been attempts to link the identified neurobiological changes to the specific features that constitute PTSD, such as altered mechanisms of learning and extinction, sensitization to stress, and arousal. Furthermore, there have been efforts to understand whether certain neurobiological changes in PTSD reflect preexisting vulnerability factors rather than consequences of trauma exposure or correlates of PTSD. Genetic variability, sex differences, and developmental exposures to stress influence neurobiological systems and moderate PTSD risk. On the basis of these findings, important hypotheses for developing novel strategies to identify subjects at risk, promote resilience, and devise targets for the prevention or treatment of PTSD can be derived.