This paper outlines a conceptual and operational framework for understanding the relationships between school culture and teenage substance use (smoking, drinking and illicit drug use). The framework draws upon Bernstein's theory of cultural transmission, a theory of health promoting schools and a frame for understanding the effects of place on health. It is proposed that the strength/weakness of classification (boundaries within school and between the school and outside world) and framing (communication) determine each school's (1) organisation, curriculum and pedagogic practice and (2) valued school identities and school-oriented learning opportunities for cognitive and affective development. These identities and learning opportunities are based either on performance or personal development and social relations. Likely teacher/student identity pairings in schools promoting performance and schools promoting personal development and social relations are discussed. Schools promoting performance-based identities and opportunities may potentially have higher school-level substance use. Students adopting a valued school identity are at lowest risk of substance use. Students who are unwilling/unable to adopt a valued school identity and disengage with school-oriented learning opportunities for cognitive and affective development are at highest risk of substance use. The potential pathways through which identified contextual (structural), collective (sociocultural) and compositional (individual-level) factors may modify these relationships through school-level and individual-level meaningfulness are described. Finally, school culture-based interventions that draw on the framework outlined in this paper that may positively affect student substance use across schools are discussed.