Presented is a conceptual framework linking the construct of temperament with environmental factors that covary with the onset and escalation of substance use. We propose that transactions between temperament characteristics of the child in family and peer contexts influence the development of self-control ability, a mediating factor for onset and possible transition to abuse in later adolescence. Risk-promoting dimensions may influence the emergence of self-control by amplifying relationship processes that detract from competence development. Emergence of good self-control can serve as a resilience factor and is linked with health-promoting cognitions. We also suggest that temperament and self-control moderate links between parenting, peer associations, and substance use. Implications of the transactional model for clinical intervention and research are discussed.