Lake ecosystems are our sentinels of environmental change and their effective management is one of our key planetary challenges in the 21st century. The evolution of ecosystem science as a basis for management is reviewed using the nested set of the Laurentian Great Lakes, Lake Ontario, and the Bay of Quinte as a primary focus. Other great lakes of the world, many of which are in Canada, provide a secondary focus. Ecosystem science has a long history in the Laurentian Great Lakes with developments driven in large part by the Great Lakes Water Quality Agreement, Lake-Wide Management Plans, and Remedial Action Plans for Areas of Concern. By comparison most other large Canadian lakes have received little attention as is the case with many of the world’s great lakes. The substantial arsenal of tools and knowledge accumulated in the Great Lakes can serve as a model for other lake systems. As the range of ecosystem management problems has continued to grow, the motivating theme has shifted from restoration through rehabilitation to adaptation. The main challenge is to coalesce the many stresses we previously have sought to manage singly: land use, population growth, habitat degradation, resource exploitation, invasive species, pollutant and contaminant loadings, and, finally, climate change. Essential features of effective ecosystem-based management are: a whole system view, active adaptive management, acceptance of science-based evidence, and shared goals with common objectives. The last two may prove the greatest hurdle as society becomes ever more divided and fractious given the global onslaught of environmental and societal challenges. The Great Lakes experience shows there is hope.