Research has consistently shown that religiousness is associated with lower levels of alcohol and drug use, but little is known about the nature of adolescent religiousness or the mechanisms through which it influences problem behavior in this age group. This paper presents preliminary results from the Mid-Atlantic School Age Twin Study, a prospective, population-based study of 6–18-year-old twins and their mothers. Factor analysis of a scale developed to characterize adolescent religiousness, the Religious Attitudes and Practices Inventory (RAPI), revealed three factors: theism, religious/spiritual practices, and peer religiousness. Twin correlations and univariate behavior-genetic models for these factors and a measure of belief that drug use is sinful reveal in 357 twin pairs that common environmental factors significantly influence these traits, but a minor influence of genetic factors could not be discounted. Correlations between the multiple factors of adolescent religiousness and substance use, comorbid problem behavior, mood disorders, and selected risk factors for substance involvement are also presented. Structural equation modeling illustrates that specific religious beliefs about the sinfulness of drugs and level of peer religiousness mediate the relationship between theistic beliefs and religious/spiritual practices on substance use. Limitations and future analyses are discussed.