Prior to the Deepwater Horizon (DWH) incident on April 20, 2010, in the Gulf of Mexico, the state of knowledge concerning oil in the sea was well summarized by the third National Research Council report (National Research Council, 2003). Since that report was published, several ongoing studies have examined spills in cold and shallow waters, for example, Peterson et al. (2003) and Wiens (2013) on the legacies and lessons of the 1989 Exxon Valdez oil spill. Oil exploration and production has moved further offshore and into much deeper water in recent decades. The DWH/Macondo blowout occurred in water over 1,000 m deep, in a relatively warm near-surface water environment, and in a region where naturally occurring seeps of oil are also common. Despite ongoing general oceanographic research in the Gulf of Mexico, establishment of ocean observing systems, and several programs funded by the US Bureau of Ocean Energy Management (BOEM, formerly Minerals Management Service), prior knowledge of oceanography in the Gulf proved to be inadequate, and not fully appropriate, for this unprecedented event, as observations in the vicinity of the spill rapidly demonstrated (see Overton et al. and Passow and Hetland in this issue). Major environmental events like the DWH spill trigger a legal process called Natural Resource Damage Assessment (NRDA) that brings together federal agencies, states, and Native American tribes to evaluate the impacts of the event on natural resources, in this case, along the nation’s coast. Because there were legal and procedural constraints on resulting field programs, data collection, and other research by US federal government agencies and their contractors as well as on BP investigations, a major program of independent scientific investigations was urgently needed. Fortunately, BP quickly established the Gulf of Mexico Research Initiative (GoMRI) to address this knowledge deficit, and GoMRI has been able to support unfettered and independent research (see Colwell). This article provides an overview of the science undertaken by the GoMRI program and its management.