This is a defining moment for the Great Lakes St Lawrence region, with the opportunity to renovate the regime for ecosystem improvement, protection and sustainability. The binational Great Lakes Water Quality Agreement was first signed in 1972. The outcome of a 2007 review of the Agreement by government and citizens, resulted in a broad call for and revisions to the Agreement, so that it can once again serve as a visionary document driving binational cooperation to address long-standing, new and emerging Great Lakes environmental issues in the 21st century. A prescription for renegotiating the Agreement to generate a revitalized and sustainable future mandates that science inform contemporary public policy, third Party Mediation presses for and coordinates a deliberate negotiation, and inclusive discourse and public engagement be integral through the process.