A significant challenge exists in assessing the social and ecological impacts of development projects in a holistic and comprehensive manner. Our objective is to elucidate the linkages between ecological change and human well-being, and its importance in integrated assessment policy for development projects, using the Three Gorges Dam (China) as a case study. A collaborative research initiative was undertaken to review and synthesize published information on the ecological and human health effects of the Three Gorges Dam. Our synthesis suggests that the Three Gorges Dam has altered social-ecological dynamics of human health and ecosystem function in the Yangtze River basin with significant consequences for human well-being. Direct impacts to human well-being were grouped into four primary categories, including: (1) toxicological impacts; (2) shifting infectious disease dynamics; (3) natural hazards; and (4) social health. Social-ecological relationships were altered in complex ways, with both direct and indirect effects, positive and negative interactions, and chronic and acute impacts on human well-being. Our synthesis supports a comprehensive evaluation of development projects via integrated assessments of human and environmental consequences. This is probably best achieved through a coupled social-environmental impact assessment to ensure holistic and comprehensive analyses of expected costs and benefits. The role of research can thereby be to elucidate the linkages between ecosystems and human health to better inform the assessment process. A synthesis of the existing information on the Three Gorges suggests that this is best achieved through institutional collaboration and transdisciplinary integration of expertise.