The Deepwater Horizon (DWH) well blowout released more petroleum hydrocarbons into the marine environment than any previous U.S. oil spill (4.9 million barrels), fouling marine life, damaging deep sea and shoreline habitats and causing closures of economically valuable fisheries in the Gulf of Mexico. A suite of pollutants—liquid and gaseous petroleum compounds plus chemical dispersants—poured into ecosystems that had already been stressed by overfishing, development and global climate change. Beyond the direct effects that were captured in dramatic photographs of oiled birds in the media, it is likely that there are subtle, delayed, indirect and potentially synergistic impacts of these widely dispersed, highly bioavailable and toxic hydrocarbons and chemical dispersants on marine life from pelicans to salt marsh grasses and to deep-sea animals. As tragic as the DWH blowout was, it has stimulated public interest in protecting this economically, socially and environmentally critical region. The 2010 Mabus Report, commissioned by President Barack Obama and written by the secretary of the Navy, provides a blueprint for restoring the Gulf that is bold, visionary and strategic. It is clear that we need not only to repair the damage left behind by the oil but also to go well beyond that to restore the anthropogenically stressed and declining Gulf ecosystems to prosperity-sustaining levels of historic productivity. For this report, we assembled a team of leading scientists with expertise in coastal and marine ecosystems and with experience in their restoration to identify strategies and specific actions that will revitalize and sustain the Gulf coastal economy. Because the DWH spill intervened in ecosystems that are intimately interconnected and already under stress, and will remain stressed from global climate change, we argue that restoration of the Gulf must go beyond the traditional "in-place, in-kind" restoration approach that targets specific damaged habitats or species. A sustainable restoration of the Gulf of Mexico after DWH must: 1. Recognize that ecosystem resilience has been compromised by multiple human interventions predating the DWH spill; 2. Acknowledge that significant future environmental change is inevitable and must be factored into restoration plans and actions for them to be durable; 3. Treat the Gulf as a complex and interconnected network of ecosystems from shoreline to deep sea; and 4. Recognize that human and ecosystem productivity in the Gulf are interdependent, and that human needs from and effects on the Gulf must be integral to restoration planning. With these principles in mind, the authors provide the scientific basis for a sustainable restoration program along three themes: 1. Assess and repair damage from DWH and other stresses on the Gulf; 2. Protect existing habitats and populations; and 3. Integrate sustainable human use with ecological processes in the Gulf of Mexico. Under these themes, 15 historically informed, adaptive, ecosystem-based restoration actions are presented to recover Gulf resources and rebuild the resilience of its ecosystem. The vision that guides our recommendations fundamentally imbeds the restoration actions within the context of the changing environment so as to achieve resilience of resources, human communities and the economy into the indefinite future.