There is a dearth of research that examines the impact of family systems therapy on problems among sexually and/or physically abused youth. Given this void, differential outcome and predictors of substance use change were evaluated for abused, as compared with nonabused, runaway adolescents who were randomly assigned to family therapy or treatment as usual. Abused adolescents reported lower family cohesion at baseline, although both abused and nonabused adolescents showed similar substance use reductions. Utilizing hierarchical linear modeling, we found that substance use changed with change in cohesion over time. These findings link change in family functioning to change in adolescent substance use, supporting family systems theory. Findings suggest that a potent target of intervention involves focus on increasing positive communication interactions.