Eutrophication, increased fishing pressure, habitat destruction and invasion of non-native plants and animals have transformed Lake Simcoe and its assemblage of fishes over the past 150 years. Notable changes include die extirpation of lake sturgeon (Acipenser fulvescens), decline of muskellunge (Esox masquinongy), and failure of recruitment of lake trout (Salvelinus namaycush) and lake whitefish (Coregonus clupeaformis). Many species, including lake trout, lake whitefish, lake herring (Coregonus artedi), and yellow perch (Perca flacescens), have undergone major fluctuations in abundance. Fisheries management actions have evolved with changes in the lake ecosystem and changes in scientific knowledge. Early regulations substantially restricted the commercial fishery and imposed many of the existing controls on the sport fishery. Along period of adjustment and addition to these regulations along with reliance on supplemental stocking (i.e., stocking of a species where a self-reproducing population of that species exists) of native fish as well as introduction of non-native fish followed. In the last 3 decades, a scientific approach and ample monitoring have been established as basic requirements for making sound management decisions. Supplemental stocking of native species and stocking of non-native species have been largely replaced by stocking of native species for rehabilitation. Successful fisheries management in the future will need to address the uncertainty about the state of complex aquatic ecosystems, and identify the possible states of the system and the probable consequences of specific management actions.