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.