Neighborhood factors have been linked to HIV risk behaviors, HIV counseling and testing, and HIV medical care. However, the social-psychological mechanisms that connect neighborhood factors to HIV-related behaviors have not been fully determined. In this article we review the research on neighborhood factors and HIV-related behaviors, approaches to measuring neighborhoods, and mechanisms that may help to explain how the physical and social environment within neighborhoods may lead to HIV-related behaviors. We then discuss organizational, geographic, and social network approaches to intervening in neighborhoods to reduce HIV transmission and facilitate HIV medical care with the goal of reducing morbidity and mortality and increasing social and psychological well-being.