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The Regional Monitoring Program for Water Quality in San Francisco Bay (RMP) is a novel partnership between regulatory agencies and the regulated community to provide the scientific foundation to manage water quality in the largest Pacific estuary in the Americas. The RMP monitors water quality, sediment quality and bioaccumulation of priority pollutants in fish, bivalves and birds. To improve monitoring measurements or the interpretation of data, the RMP also regularly funds special studies. The success of the RMP stems from collaborative governance, clear objectives, and long-term institutional and monetary commitments. Over the past 22 years, high quality data and special studies from the RMP have guided dozens of important decisions about Bay water quality management. Moreover, the governing structure and the collaborative nature of the RMP have created an environment that allowed it to stay relevant as new issues emerged. With diverse participation, a foundation in scientific principles and a continual commitment to adaptation, the RMP is a model water quality monitoring program. This paper describes the characteristics of the RMP that have allowed it to grow and adapt over two decades and some of the ways in which it has influenced water quality management decisions for this important ecosystem.