Children whose parents or caregivers use drugs or alcohol are at increased risk of short- and long-term sequelae ranging from medical problems to psychosocial and behavioral challenges. In the course of providing health care services to children, pediatricians are likely to encounter families affected by parental substance use and are in a unique position to intervene. Therefore, pediatricians need to know how to assess a child’s risk in the context of a parent’s substance use. The purposes of this clinical report are to review some of the short-term effects of maternal substance use during pregnancy and long-term implications of fetal exposure; describe typical medical, psychiatric, and behavioral symptoms of children and adolescents in families affected by substance use; and suggest proficiencies for pediatricians involved in the care of children and adolescents of families affected by substance use, including screening families, mandated reporting requirements, and directing families to community, regional, and state resources that can address needs and problems. (Author abstract)