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Posttraumatic stress disorder (PTSD) is an unusual diagnosis in requiring an external environmental stressor to be present, in addition to the conventional signs and symptoms. Early controversies surrounded the validity of its criteria and whether there was a common neural basis for this disorder. This review summarizes recent neuroimaging studies, which have begun to clarify the basis of PTSD by combining imaging data with investigations of the stress response, and by employing fear and extinction learning paradigms to probe the underlying neural changes in those with the disorder.We examine the recent literature with three main aims. First, to assess whether structural changes in PTSD are causal of or secondary to the condition. Second, to summarize current understanding of the relationship between neural activation and the stress responses within the autonomic nervous system in PTSD patients and controls. Finally, we examine neural mechanisms underlying the response to fear and reward, demonstrating how these are altered in PTSD.A greater understanding of the brain mechanisms underlying healthy responses to fear and stress, and their alterations in PTSD, has opened up a new spectrum of possible pharmacological agents by which to approach to PTSD therapy and has begun to reveal the neural processes underlying the common failure of response to current treatments.