Preclinical work in our laboratory at the UT Southwestern Medical Center has established that corticosterone can dose-dependently reduce an established fear memory in rodents. In this study, mice were trained to associate foot-shock with a specific training context to induce fear memory. When this fear memory was reactivated by the contextual stimulus and then followed by glucocorticoid administration, subsequent reactivation of the fear memory produced significantly less fear responses relative to mice administered saline after memory reactivation. After only one pairing of reactivation and glucocorticoid, this effect was reversible with a subthreshold reminder shock and was transient, indicating that the effect of glucocorticoids was on the extinction process. These results strongly suggested glucocorticoid treatment paired with therapeutic traumatic memory reactivation as a specific therapy for PTSD in humans and directly informed our pilot studies in PTSD patients.