The Green Bay watershed, draining a total area of approximately 40,468 km2, comprises about a third of the Lake Michigan drainage. In the early years, fur trade was the dominant economic activity within the watershed. Later, when timber harvesting, papermaking, and agriculture came on the scene in the 19th and early 20th centuries, major environmental changes occurred in a relatively short period of time. Nutrient and sediment loadings, accompanied by organic wastes from sawmills and paper mills, resulted in a pollutant overload in the Fox River and in the eutrophication of the waters of lower Green Bay. Citizen complaints about these severely degraded conditions initiated a period of scientific investigation. Starting slowly with a few studies and surveys in the first half of the 20th century, serious investigatory work began at mid-century with support from the University of Wisconsin Sea Grant Institute. Examples of topics that have been investigated since then with support from numerous sources are: biological oxygen demand (BOD), phosphorus and total suspended solids loads, trophic status and food chain efficiencies, coastal wetland characterization, dynamics of the benthic layer, algae and abiotic solids, phosphorus cycling and mass balance, PCBs, seasonal hypoxia, and climate change impacts. These studies have provided the scientific foundation for government-led programs such as the Green Bay Remedial Action Program, the PCB clean-up program, and the TMDL program. Progress has been made—reduction in BOD is an example—but a fuller rehabilitation of this large-scale ecosystem remains an elusive goal. The saga goes on.