In this paper, the prevalence of child and adolescent substance use is briefly presented. The nature of the co-occurrence of multiple antisocial behaviors, including substance use, during adolescence, and the causal factors which contribute to the early onset and maintenance of youth substance use and substance abuse are discussed. Emphasis is placed on parent and family factors, and children's social competence, which are associated with substance use, and which are the potentially mutable targets of family-based preventive interventions. Family-based preventive interventions were classified as either primarily addressing parent and family skills training, or addressing family therapy and in-home family support models. Distinctions were also made between programs that were universal or selective preventive interventions, or that were indicated preventive interventions directed at high risk individuals who were already showing early signs of being on the trajectory to substance abuse. Intervention research conducted within the past 30 years within these topical areas are summarized within tables, and findings indicate consistent intervention effects on children's problem behaviors, and on potential mediating processes such as parenting behaviors and aspects of family functioning. Recent studies with strong designs are described in greater depth. The paper concludes with discussions of the gaps in current intervention research, of barriers encountered in the implementation and evaluation of family-based prevention programs, and of the implications for future preventive intervention research and for social policy related to family-based preventive interventions.