Despite the high prevalence of the psychoactive substance use disorders (PSUDs), relatively little is known about the childhood antecedents of these disorders. To examine this issue a comprehensive review of the English-language literature on studies of preadolescents (< 12 years) who subsequently developed PSUDs or were offspring of parents with PSUDs was undertaken. In all, nine longitudinal studies and 13 cross-sectional studies were identified. Data from studies of subjects at high risk for PSUDs indicate that children of parents with PSUDs are at increased risk for the development of temperamental, personality, non-PSUD psychiatric, cognitive, and psychosocial disturbances. Longitudinal studies also indicate that children with these neuropsychiatric disturbances are at increased risk for the development of PSUDs in adolescence and adulthood. We conclude that neuropsychiatrically impaired children of parents with PSUDs may represent those at highest risk for later development of PSUDs. Because these neuropsychiatric disorders are potentially treatable, their identification may lead to effective early intervention strategies.