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Water quality monitoring is a cornerstone of environmental protection and ambient monitoring provides managers with the critical data they need to take informed action. Unlike site-specific monitoring that is at the heart of regulatory permit compliance, regional monitoring can provide an integrated, holistic view of the environment, allowing managers to obtain a more complete picture of natural variability and cumulative impacts, and more effectively prioritize management actions. By reviewing four long-standing regional monitoring programs that cover portions of all three coasts in the United States–Chesapeake Bay, Tampa Bay, Southern California Bight, and San Francisco Bay–important insights can be gleaned about the benefits that regional monitoring provides to managers. These insights include the underlying reasons that make regional monitoring programs successful, the challenges to maintain relevance and viability in the face of ever-changing technology, competing demands and shifting management priorities. The lessons learned can help other managers achieve similar successes as they seek to establish and reinvigorate their own monitoring programs.