OBJECTIVES: Within the socio-ecologic framework, diet and physical activity are influenced by individual, interpersonal, organizational, community, and public policy factors. A basic principle underlying this framework is that environments can influence an individual's behavior. However, in the vast majority of cross-sectional and even the few longitudinal studies of this relationship, the question of whether individuals select their area of residence based on physical activity-related amenities is ignored. In this paper, we address a critical methodological issue: self-selection of residential location, which is generally not accounted for, and can significantly compromise research on the relationship between environmental factors and physical activity behaviors. METHOD: We define and discuss the problem of residential self-selection in the study of neighborhood influences on health and health behavior, review methods used to control for residential self-selection in the literature, and present our strategy for addressing this potentially important source of bias. CONCLUSION: Existing research has built our understanding of residential self-selection bias, but important gaps remain. Our strategy uses data from a longitudinal cohort study linked to contemporaneous environmental measures to create a multi-equation model system to simultaneously estimate residential choice, environmental influences on physical activity, and downstream health outcomes such as obesity and clinical cardiovascular disease risk factor measures.