Integrated assessment and management of water resources for the supply of potable water is increasingly important in light of projected water scarcity in many parts of the world. This article develops frameworks for regional-level waterborne human health risk assessment of chemical and microbiological contamination to aid water management, incorporating economic aspects of health risks. Managed aquifer recharge with surface water from a river in Southern Finland is used as an illustrative case. With a starting point in watershed governance, stakeholder concerns, and value-at-risk concepts, we merge common methods for integrative health risk analysis of contaminants to describe risks and impacts dynamically and broadly. This involves structuring analyses along the risk chain: sources-releases-environmental transport and fate-exposures-health effects-socio-economic impacts-management responses. Risks attributed to contaminants are embedded in other risks, such as contaminants from other sources, and related to benefits from improved water quality. A set of models along this risk chain in the case is presented. Fundamental issues in the assessment are identified, including 1) framing of risks, scenarios, and choices; 2) interaction of models and empirical information; 3) time dimension; 4) distributions of risks and benefits; and 5) uncertainties about risks and controls. We find that all these combine objective and subjective aspects, and involve value judgments and policy choices. We conclude with proposals for overcoming conceptual and functional divides and lock-ins to improve modeling, assessment, and management of complex water supply schemes, especially by reflective solution-oriented interdisciplinary and multi-actor deliberation.