Efforts of federal, state and local governments, working in partnership through the Chesapeake Bay Program along with the Chesapeake Bay Foundation and other nonprofit environmental groups, to restore or at least maintain the current water quality, have had mixed results. One particular obstacle to cleaning up the bay is that much of the polluting substances are discharged far upstream in states far removed from the bay: New York and Pennsylvania. Despite the State of Maryland spending over $100 million to restore the bay, conditions have continued to grow worse. In the mid-20th century, the Bay supported over 6,000 oystermen. As of 2008, there were fewer than 500.
In June 2000, the Chesapeake Bay Program adopted Chesapeake 2000, an agreement adopted by the member jurisdictions, intended to guide restoration activities throughout the Chesapeake Bay watershed through 2010. One component of this agreement was a series of upgrades to sewage treatment plants throughout the watershed. In 2016 EPA stated that the upgrades "have resulted in steep reductions in nitrogen and phosphorus pollution... despite increases in human population and wastewater volume."
EPA published a series of scientific documents on water quality criteria for the bay between 2004 and 2010. The criteria documents, which describe specific pollutants and their effects on aquatic species, are used by the states to develop water quality standards (WQS) for individual water bodies. Delaware, Maryland, Virginia, and the District of Columbia adopted WQS for various Chesapeake Bay tributaries in the mid-2000s, referencing the EPA criteria documents, as well as their own extensive data gathering and modeling efforts.
Restoration efforts that began in the 1990s have continued into the 21st century and show potential for growth of the native oyster population. Efforts to repopulate the bay using oyster hatcheries have been carried out by a group called the Oyster Recovery Partnership, with some success. In 2011 the group placed 6 million oysters on  of the Trent Hall sanctuary. Scientists from the Virginia Institute of Marine Science at the College of William & Mary claim that experimental reefs created in 2004 now house 180 million native oysters, Crassostrea virginica, which is far fewer than the billions that once existed.