The ecosystem services provided by large, complex freshwater systems have long been subjected to various stresses by humans; drinking water, transport, manufacturing, and even recreation have been impaired in different ways. How can these systems be managed to protect their health and services for present and future generations? We discuss the jurisdiction, stressors, and examples of preventative management, as well as future needs, for 2 iconic North American freshwater systems: (1) the Laurentian Great Lakes, an international system of lakes and waterways that comprise similar to 21% of the world's surface fresh water; and (2) the Florida Everglades, an ecosystem consisting of lakes, rivers, freshwater wetlands, estuaries, and marine bays, located in south Florida, and which have been heavily modified. Billions of dollars are being invested in restoration projects in both ecosystems. Despite differences in size, governance structure, and impairments, the overriding needs associated with large-scale ecosystem protection and restoration result in similar recommendations for the preventative management of these 2 systems: a robust monitoring network; early warning and detection systems; and effective enforcement of regulations.