The Pamlico Sound (PS) with its sub-estuaries is the largest lagoonal ecosystem in the United States. It exhibits periodically strong salinity stratification and an average freshwater residence time of 1 year for the sound proper. This relatively long residence time promotes effective use and cycling of nutrients, allowing the system to support high rates of primary and secondary production, and serve as a vitally important fisheries nursery. This hydrologic characteristic also makes the system highly sensitive to nutrient over-enrichment and eutrophication. The PS is experiencing ecological change in response to increasing human activity and climatic perturbations. Human impacts include a rise in nutrient, sediment, and other pollutant loads that accompany urbanization and agricultural and industrial growth in its watersheds and airsheds. Since the mid-1990s, the PS has witnessed a sudden rise in tropical storm and hurricane impacts, with eight hurricanes and four tropical storms having made landfall in the PS watershed during the 1996 to 2007 period. Each of these storms had unique hydrologic, nutrient, and other pollutant loading effects. In addition, since the early 2000s, the region has experienced record droughts, which are continuing. Variable freshwater discharges from storms and droughts have caused large oscillations in nutrient enrichment, reflected ultimately in differential phytoplankton production, biomass, and community compositional responses. Floodwaters from the two wettest hurricanes, Fran (1996) and Floyd (1999), and from Tropical Storm Ernesto (2006) exerted long-term (months) effects on hydrology, nutrient loads, and algal production. Windy but relatively dry hurricanes, like Irene (1999) and Isabel (2003), caused strong vertical mixing, storm surges, but relatively minor changes in river flow, flushing, and nutrient loads. These contrasting effects are accompanied by biogeochemical (hypoxia, nutrient cycling) and habitat alterations, and associated food web disturbances. Each storm type influenced algal growth and compositional dynamics; however, their respective ecological impacts differed substantially. Changes in hydrologic and wind forcing resulting from changes in frequency and intensity of storms and droughts strongly influence water and habitat quality. These changes must be integrated with nutrient loading/dilution effects when assessing and predicting ecological responses to nutrient and hydrologic variability on this and other large lagoonal ecosystems.