In 2010 the Deepwater Horizon explosion and fire in the Gulf of Mexico caused the largest offshore oil spill in U.S. history, resulting in significant impacts on the region's environment and residents. Legal settlements with the companies held responsible led the federal government to ask the National Academy of Sciences to form and administer a 30-year program to enhance oil system safety, human health, and environmental resources in the Gulf of Mexico and other U.S. continental shelf areas where offshore oil and gas exploration and production occur or are under consideration. The new Gulf Research Program will receive $500 million to support activities using three broad approaches: research and development, education and training, and environmental monitoring. The Gulf Research Program: A Strategic Vision establishes the Program's foundation and introduces its mission, goals, and objectives. It describes some initial activities and sets out the Program's vision for contributing lasting benefit to the Gulf region and the nation. The Program is an extraordinary opportunity to foster science on a regional scale and over the long term. The document will be of interest to scientists, health professionals, engineers, and educators who wish to learn about, collaborate with, and submit proposals to the Program, and to all those who share the goal of enhancing resilience in areas where offshore energy production, vibrant communities, and dynamic ecosystems coexist.