The United States has a complex, multi-agency structure to plan, synchronize, and execute foreign policy and national security. By statute, the State Department is the lead agency for foreign policy. However, in practice, the much larger and better-funded Department of Defense conducts much of America's foreign policy activity, often with little coordination with the State Department or other relevant agencies. Over the past two decades, the military's Geographic Combatant Commands have taken an increasing lead in planning and executing foreign policy activities around the world. This has often effectively put a military face and voice on America's foreign policy, sometimes to the detriment of broader U.S. goals and relationships. More effective U.S. foreign policy requires greater interagency coordination at all levels and a greater role for the State Department as America's lead agency for foreign policy. This study examines current interagency structures, focused particularly on the regional and sub-regional levels, describes several current or recent shortfalls in interagency unity of effort, and surveys the interagency reform literature. This study then suggests a typology of interagency reform proposals, analyzes the potential reforms, and recommends a new model: a State Department-led regional interagency headquarters. This U.S. Regional Mission would lead all U.S. foreign policy activities in the region, including the activities of the Geographic Combatant Command and the U.S. embassies in the region. The U.S. Regional Mission would conduct sub-regional operations by creating Interagency Task Forces, which would be headed by a leader from the department or agency most appropriate to the mission.