Built environments that support walking and other physical activities have the potential to reduce cardiovascular disease (CVD). Walkable neighborhoods-characterized by density, land use diversity, and well-connected transportation networks-have been linked to more walking, less obesity, and lower coronary heart disease risk. Yet ongoing research on pedestrian-friendly built environments has the potential to address important gaps. While much of the literature has focused on urban form and planning characteristics, additional aspects of street-scapes, such as natural and architectural amenities, should also be considered. Promising future directions include (1) integration of multiple built environment measures that facilitate an understanding of how individuals perceive and act within their environment; (2) examination of both the daily physical activities that are most feasibly influenced by the local environment and those more deliberate or vigorous patterns of physical activity that are most predictive of CVD; (3) consideration of multiple pathways that could mediate a link between walkability and CVD, including not only physical activity, but also air quality improvements from reduced vehicle mileage and enhanced neighborhood social cohesion from unplanned interactions; (4) testing competing hypotheses that may explain interactions of built environment characteristics with each other and with personal barriers to walking; (5) stronger conceptualization of the multiple neighborhoods or activity spaces that structure opportunities for physical activity throughout the day; (6) collecting and strategically analyzing longitudinal data to support causal inference; and (7) studying neighborhood preferences and selection to move beyond biased assessments of neighborhood health effects. While walkability has been linked to health-related behaviors and CVD risk factors, the implications of the observed correlations are not yet clear. New theoretical insights, measurement technologies, and built environment changes represent opportunities to enhance the evidence base for bringing health promotion and cardiovascular disease prevention into the conversation about how communities are planned and built.