The Great Lakes coastal region is a dynamic area at the interface between land and water. It is heavily influenced by the magnitude of the large lakes themselves, by natural abiotic and biotic processes in the watershed, and especially by human activity. This special issue contains a series of 21 papers that are organized into four major themes: 1) landscape characterization and coastal linkage, 2) integration, 3) indicator development, and 4) supporting information. The results of these papers emphasize that many environmental response signals are linked to their physiobiogeographic location in the basin and with human activity in coastal watersheds or in the immediate coastal margin. If lake levels continue to fluctuate and decline, if the climate continues to warm, if agricultural activity expands, if exotic species continue to invade, and if the human population density in the watershed increases, then environmental indicators of the Great Lakes coastal region reported here will point to further degradation of water quality and native amphibian, bird, diatom, fish, macroinvertebrate, and wetland plant communities. These environmental indicators are benchmarks for the current conditions of the Great Lakes coastal region and provide measurable endpoints to assess the success of future management, conservation, protection, and restoration of this important resource.