This study examined the relation between witnessing violence and drug use initiation among 6th graders attending middle schools in 5 rural counties and investigated the extent to which family support and parental monitoring moderated this relation. Data were obtained from 1,282 adolescents at 2 time points during the 6th grade. Witnessing violence predicted subsequent initiation of cigarette, beer and wine, liquor, and advanced alcohol use. Adolescents who reported high levels of family support and parental monitoring were less likely to initiate use across all drug categories except beer and wine. High levels of parental monitoring and family support were effective in buffering the relation between witnessing violence and initiation of cigarette and advanced alcohol use at low levels of witnessing violence. With increasing levels of witnessing violence, however, the protective effects of monitoring and support were substantially diminished. These findings have important implications for research and intervention efforts.