A significant proportion of military personnel deployed in support of Operation Enduring Freedom (OEF) and Operation Iraqi Freedom (OIF) has been exposed to war-zone events potentially associated with traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD). There has been significant controversy regarding healthcare policy for those service members and military veterans who returned from OEF/OIF deployments with both mild TBI and PTSD. There is currently little empirical evidence available to address these controversies. This review uses a cognitive neuroscience framework to address the potential impact of mild TBI on the development, course, and clinical management of PTSD. The field would benefit from research efforts that take into consideration the potential differential impact of mild TBI with versus without persistent cognitive deficits, longitudinal work examining the trajectory of PTSD symptoms when index trauma events involve TBI, randomized clinical trials designed to examine the impact of mild TBI on response to existing PTSD treatment interventions, and development and examination of potential treatment augmentation strategies.