The overlap in clinical phenomenology and morbidity between post-traumatic stress disorder (PTSD) and such conditions as major depression, anxiety disorders and aggression, in which a serotonin dysfunction is implicated, suggests a role for serotonin in the pathophysiology of PTSD. In this paper, we review current knowledge concerning the role of serotonergic mechanisms and interventions in PTSD. Since there is no clearly effective pharmacologic intervention for this disorder, the underlying neurochemical dysfunction needs to be carefully defined so that more effective treatment can be developed. Preclinical and clinical studies of the serotonergic mechanisms in the pathophysiology of PTSD and treatment trials involving serotonergic agents are limited, but indicate considerable promise. Further investigation of a serotonergic dysfunction in PTSD and of its treatment with serotonergic agents is warranted.