The Controlling Asthma in American Cities Project (CAACP) was designed to improve the control of asthma in inner-city populations of children with a disparate burden of symptoms and adverse outcomes. As with many chronic diseases, asthma is the manifestation of multiple biologic, environmental, and social determinants. In addition to appropriate medical management, individuals with asthma must have logistical, financial, and cultural access to environments that allow avoidance of asthma triggers and encourage good asthma management practices. In recognition of this complexity, the CAACP required the seven project sites to coordinate and synchronize multiple interventions (education, healthcare access, medical management, trigger reduction) at multiple levels (individual, home, school, community, and policy) through the collaboration of relevant groups, institutions, and individuals. This paper describes the “program theory” of the CAACP project-the assumptions about how the project worked, how the components were linked, and what outcomes were anticipated. It relates the subsequent papers in the supplement to the program theory and describes how the papers can inform and guide other community-based interventions, and advance the translation of scientific knowledge to effective interventions in communities of need.