Since their inception in the 1940s, the Department of Energy (DOE) national laboratories have been in the vanguard of America’s global research and development leadership. However, the national innovation system has changed in the past 70 years. Today, much technology development and application occurs in the context of synergistic regional clusters of firms, trade associations, educational institutions, private labs, and regional economic development organizations. Unfortunately, legacy operating procedures limit the DOE labs’ ability to engage fully with the regional economies in which they are located. This lack of consistent engagement with regional technology clusters has likely limited the labs’ overall contributions to U.S. economic growth.