Associations between witnessing serious violence and drug use, and the protective influences of family cohesion and parental monitoring, were investigated among 9,840 adolescents (50.5% female, M age=15.29 years, SD=1.76) living in Panama and Costa Rica. After accounting for demographics and parental and sibling substance use, witnessing serious violence was associated with greater drunkenness, tobacco use, number of illicit drugs used, and problems with drugs and alcohol. In every analysis, exposure to violence was associated with more drug use, while family cohesion and parental monitoring attenuated risk. Further, family cohesion and parental monitoring exerted a protective-stabilizing effect on number of illicit drugs used and on problems with drugs and alcohol. There were few interactions with age. Implications for prevention are discussed.