This paper reviews the currently available knowledge about the psychobiology and psychopharmacology of post-traumatic stress disorder (PTSD). It also reviews the various studies that have elucidated changes in brain function and structure in PTSD populations, including position emission tomography (PET), single photon emission computed tomography (SPECT), and event-related potential (ERP) studies. It then reviews the literature on catecholamine and hypothalamic-pituitary-adrenal (HPA) axis abnormalities in PTSD, and finally reviews the literature available on the psychopharmacology of PTSD. It discusses how the pathophysiology of PTSD determines the nature of psychopharmacological interventions. Psychopharmacological interventions in PTSD are largely limited to good studies on the effects of the selective serotonin reuptake inhibitors (SSRIs). In order to effectively intervene in PTSD, studies of other psychopharmacological agents are necessary, specifically of agents which affect limbic activation, decreased frontal lobe functioning, altered HPA activity, and other biological features of PTSD. Copyright 2001 John Wiley & Sons, Ltd.