Much attention has been given to the role of catecholamine dysfunction in posttraumatic stress disorder (PTSD), and only recently have researchers begun to focus on serotonin (5-HT) in PTSD. Serotonin appears to be a factor in responses followin extreme stress, such as those that precede PTSD. In this review, the authors provide a brief overview of the concept of PTSD and specific issues of clinical concern. The role 5-HT in the neurobiology of PTSD is explored in a review of animal model studies and of clinical investigations of paroxetine binding, pharmacologic challenges, and neuroimaging. Data on the use of 5-HT in PTSD treatment are provided in a review of both open-label and controlled studies of serotonergically active drugs. © 1998, Cambridge University Press. All rights reserved.