The purpose of this study was to provide a descriptive profile of the alcohol, cigarette, marijuana and cocaine use practices among adolescents and to examine the relationship between employment, political beliefs, religious beliefs and substance use behaviors among high school seniors participating in the Monitoring the Future Study during the 2002 academic school year. Data from the Monitoring the Future (MTF) study (2002 12th grade core data) was used for this study. Logistic regression models were used to examine the relationship between substance use behaviors and employment, political beliefs, and religiosity. Analysis showed that males and females who believed religion was very important were less likely to have initiated alcohol use, to be a current user, and to have binge drank. A significant association was found for all alcohol use variables for those individuals who worked moderate amounts at an after school job. Political beliefs were found to be associated for initiation and current alcohol use but not for binge drinking. Political beliefs, religion, and employment were all significantly associated with cigarette use and cocaine use. Conceptualization of substance use behavior and its prevention and treatment should include consideration of such key cultural and social factors as religiosity, employment and political beliefs of adolescents.