This chapter reviews evidence concerning familial influences on the development of offspring substance use disorders (SUDs). Familial influences are diverse and operate on multiple levels, including heritable individual differences, parent–child relationships, parenting practices (both general and substance use-specific), sibling influences, and the effects of the broader family environment. Moreover, familial factors both influence and interact with other social contextual influences on offspring substance use outcomes, including peer groups, schools, and neighborhoods. Thus, familial influences operate across development, on multiple levels, and within complex, multivariate, mediated, and moderated pathways to influence offspring substance use outcomes from initial substance use onset to the remediation of clinical SUDs.