Human Performance Optimization (HPO) has drawn considerable attention within the Department of Defense (DoD). In January 2004, the Deputy Secretary of Defense issued a policy memorandum stating that the Military Health System (MHS) must develop programs to optimize human performance. This statement generated significant interest, and was again emphasized in the DoD Quadrennial Review Report 2006, with specific dictates for the MHS to address gaps in the area of human performance enhancement, in particular as directly related to mission requirements. In May 2005, the director of the Office of Net Assessment (ONA) distributed an innovative report entitled "Human Performance Optimization and Military Missions." This report was based upon interviews with various operational units, as well as discussions among various medical and research persons within the Department of Defense who were working in the area of human performance. The ONA report resulted in Health Affairs requesting Uniformed Services University (USU) to host a conference to initiate the development of a strategic plan for HPO in DoD. The conference was held 7-9 June 2006. The conference concluded with specific recommendations identifying urgent requirements to organize, coordinate, and integrate the HPO process in the DoD. This report was presented to the Assistant Secretary of Defense for Health Affairs, and the Deputy Assistant Secretary of Defense for Force Health Protection and Readiness was asked to address the principal questions of where does HPO in the DoD need to go, who will do it, and how will it be done. On 14 and 15 November another ONA sponsored meeting was held to discuss HPO in DoD. Multiple DoD agencies and services were assembled and the group consensus validated the USU-generated HPO report. USU faculty members Francis G. O'Connor, COL, MC, and Dr. Patricia Deuster, PhD, MPH, have been actively involved in the Health Affairs planning process that is presently charting a future course for HPO in the military. Drs. O'Connor and Deuster have forwarded a detailed proposal to nominate USU as home to a future HPO "clearinghouse", envisioned as a state-of-the-art translational research center. Together with the DoD movement in the area of HPO, this report outlines a proposal to organize and structure the University's effort in this arena, and to move forward in our continuing effort to "Care for those in Harm's Way".