Data were drawn from the 2002 Monitoring the Future survey, which collected self-report information from 2,258 high school seniors within the 48 contiguous States. The primary goal of the current research was to estimate a descriptive profile of the alcohol, cigarette, marijuana, and cocaine use behaviors among high school seniors and to explore the relationship between high school drug use behavior and religiosity, employment status, and political beliefs. Results of logistic regression analyses indicated that a high degree of religiosity in both male and female adolescents was related to lower alcohol initiation rates, lower current use rates, and lower binge drinking rates. Employment was also significantly related to all alcohol use variables for adolescents who worked moderate amounts after school. Initiation and current alcohol use were associated with political beliefs and cigarette and cocaine use were significantly related to political beliefs, degree of religiosity, and employment. The findings suggest that the development of prevention and treatment options should be sensitive to key cultural and social factors, such as religiosity, employment, and political beliefs during adolescence. Future research should focus on understanding how political beliefs influence substance use among adolescents. Tables, references