Management of the northern Gulf of Mexico large hypoxic zone is driven primarily by the Mississippi River/Gulf of Mexico Watershed Nutrient Task Force (Hypoxia Task Force) Action Plan. Both the 2001 and revised 2008 Action Plans called for a reduction in the average areal extent of the hypoxic zone to 5000 km2 by the year 2015, less than 1/3 the current typical annual maximum area. To achieve this goal, watershed nutrient loading reductions of 45% total nitrogen and 45% total phosphorus were estimated needs. The science to inform these targets and develop hypoxia mitigation strategies was derived from predictive models based on the quantitative relationship between causative factors (e.g. nutrient loading, stratification) and extent of hypoxia, long-term monitoring, and forecast models to test the validity of predicted relationships. This science provided the foundation for an evaluation by an Environmental Protection Agency Science Advisory Board Hypoxia Advisory Panel which served to update and synthesize research efforts on the causes and consequences of the hypoxic zone and assess progress in implementing nutrient reduction measures in the Mississippi River watershed. This information subsequently led to the adoption of the 2008 Action Plan by the Hypoxia Task Force.