The implementation of the Affordable Care Act of 2010 and the Obama administration’s urban policy create an opportunity to link community development with health in new and powerful ways. New federal programs, such as the Affordable Care Act’s Community Transformation Grants, seek to prevent death and disability through policy, environmental, programmatic, and infrastructure changes. But fragmented congressional jurisdiction and budget “scoring” rules pose challenges to needed reform. We argue that government agencies need to adopt so-called systems of innovation, or organizational practices and support mechanisms that seek continuously to test new models, refine promising ones, bring to scale those that work best, and restructure or terminate what does not. We also argue that a strong and well-focused policy advocacy coalition is needed to help drive reform focused on the social determinants of health.