Glucocorticoids are of special interest for the prevention and treatment of post-traumatic stress disorder (PTSD) because they affect memory processes that are involved in the pathophysiology, symptomatology and treatment of this disorder. Administered soon after a traumatic event, high doses of glucocorticoids may have preventive effects with regard to the development of the disorder by interfering with initial consolidation of the trauma and/or by reducing aversive memory retrieval. Further, glucocorticoids could be used in existing PTSD to reduce the retrieval of aversive memories and thus to curtail the expression of fear, such as of flashbacks. Finally, moderate doses of glucocorticoids could be used to augment the consolidation of extinction memory in patients who undergo extinction-based psychotherapy. Below, we review clinical studies that used glucocorticoid signalling-based interventions to prevent or treat PTSD. Because of the rather small sample sizes of these studies, only weak recommendation for the use of glucocorticoids in the prevention or treatment of PTSD can be made so far.