The authors systematically reviewed 42 quantitative studies on the relationship between media exposure and tobacco, illicit drug, and alcohol use among children and adolescents. Overall, 83% of studies reported that media was associated with increased risk of smoking initiation, use of illicit drugs, and alcohol consumption. Of 30 studies examining media content, 95% found a statistically significant association between increased media exposure and negative outcomes. Similarly, of the 12 studies evaluating the quantity of media exposure, 67% reported an association with a negative outcome. Overall, all 17 of the identified longitudinal studies supported a causal association between media exposure and negative outcomes over time. The evidence was strongest for links between media exposure and tobacco use; it was moderate for illicit drug use and alcohol use. Substantial variability in methodological rigor across studies and expanding definitions of media exposure contribute to persistent gaps in the knowledge base. (Contains 5 tables.)