Social interaction learning theory provides a framework for understanding the potential overlap among adolescent problem behaviors such as family violence, aggression, and substance use. The current study assessed the longitudinal, reciprocal relations among family violence, bullying perpetration, fighting perpetration, and adolescent substance use using a sample of 1,232 students from four Midwestern middle schools. Students completed measures on family dynamics, bullying and fighting behaviors, and alcohol and drug use three times over 18 months. Structural equation modeling results indicated that bullying and fighting perpetration mediated the link between family violence and substance use only for males, but not for females. For females, family violence at Wave 1 was related to greater substance use at Wave 3.