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The overarching goal of this article is to make explicit the multiple pathways through which the built environment may potentially affect health and well-being. The loss of close collaboration between urban planning and pulic health professionals that characterized the post-World War II era has limited the design and implementation of effective intervention and policies that might translate into improved health for urban populatons. First, we present a conceptual model that developed out of previous research called Social Determinants of Health and Environmental Health Promotion. Second, we review empirical research from both the urban planning and public health literature regarding the health effects of housing and housing interventions. And third, we wrestle with key challenges in conducting sound scientific research on connections between the built environment and health, namely: (1) the necessity of dealing with the possible health consequences of myriad public and private sector activities; (2) the lack of valid and reliable indicators of the built environment to monitor the health effects of urban planning and policy decisions, especially with regard to land use mix; and (3) the growth of the “megalopolis” or “super urban region” that requires analysis of health effects across state lines and in circumscribed areas within multiple states. We contend that to plan for healthy cities, we need to reinvigorate the historic link between urban planning and public health, and thereby conduct informed science to better guide effective public policy.