The current wars in the Middle East have resulted in between 10-20% of U.S. service members with mild traumatic brain injury (mTBI). While anecdotal reports have associated hyperbaric oxygen (HBO2) with improved outcomes after mTBI, controlled research is lacking. The Department of Defense (DoD), in collaboration with the Department of Veterans Affairs (DVA), has a comprehensive program examining this issue. The DoD's four randomized controlled trials will enroll a total of 242 service members with post-concussion syndrome and expose them to a range of control, sham and HBO2 conditions for 40 sessions over a period of eight to 11 weeks. Compression pressures will range from 1.2 atm abs (sham) to 2.4 atm abs, and oxygen concentration will range from room air (sham and control) to 100%. Outcomes measures include both subjective and objective measures performed at baseline, at exposure completion, and at three to 12 months' follow-up. This integrated program of clinical trials investigating the efficacy of HBO2 in service members with persistent symptoms following mTBI exposure will be important to define practice guidelines and, if needed, for the development of definitive clinical trials in this population.