The U.S. EPA Great Lakes National Program Office (GLNPO) implements long-term monitoring programs to assess Great Lakes ecosystem status and trends for many interrelated ecosystem components, including offshore water quality as well as offshore phytoplankton, zooplankton and benthos; chemical contaminants in air, sediments, and predator fish; hypoxia in Lake Erie's central basin; and coastal wetland health. These programs are conducted in fulfillment of Clean Water Act mandates and Great Lakes Water Quality Agreement commitments. This special issue presents findings from GLNPO's Great Lakes Biology Monitoring Program, Great Lakes Water Quality Monitoring Program, Lake Erie Dissolved Oxygen Monitoring Program, Integrated Atmospheric Deposition Network, Great Lakes Fish Monitoring and Surveillance Program, and Great Lakes Sediment Surveillance Program. These GLNPO programs have generated temporal and spatial datasets for all five Great Lakes that form the basis for assessment of the state of these lakes, including trends in nutrients, key biological indicators, and contaminants in air, sediments and fish. These datasets are used by researchers and managers across the Great Lakes basin for investigating physical, chemical and biological drivers of ongoing ecosystem changes; some of these analyses are presented in this special issue, along with discussion of new methods and approaches for monitoring.