Post-traumatic stress disorder (PTSD) is a devastating and costly psychological condition that is a consequence of exposure to a severe traumatically stressful event, as regularly occurs in a combat situation. The hallmark symptoms of PTSD - social withdrawal, re-experiencing, generalized anxiety and stress-sensitization - all can be viewed as manifestations of abnormally persistent, powerful, and pathologically enhanced memory of the trauma. These symptoms of PTSD take some time to consolidate, and by the time a diagnosis can be made, available treatments are almost completely ineffective, resulting in a lifelong and debilitating condition that compromises the return to a healthy productive life after combat. There is evidence from epidemiological studies for an association between early life stress and increased vulnerability to PTSD later in life. However, the biological mechanisms have not been adequately explored. These studies will use rat models of early life stress to define the types of stress and the potential utility of using an easily administered antidepressant drug treatment to reverse the changes that occur early in life that increase vulnerability to PTSD during adulthood. If our results with the antidepressant drug sertraline are promising, then it is possible that clinical trials could begin to assess the effects of early intervention with sertraline or other antidepressants could be initiated. Depending on the outcome of the clinical trials, this may eventually lead to better targeted treatments for PTSD.