Large epidemiological studies have shown that the prevalence of substance misuse (e. g., early initiation, binge drinking, illegal drug use) varies considerably among adolescents from different countries or regions (Currie et al., 2004). However, the underlying reasons for these differences are not necessarily known. The developmental sciences have attempted to explain the progression of adolescent problem behaviours, such as misuse of psychoactive substances (Silbereisen & Weichold, in press). For example, an imbalance between risk and protective factors is believed to engender behavioural problems, and certain national or cultural differences may help explain this relationship. A variety of personal risk factors that increase the probability of adolescent substance misuse have been identified in prior research. It is believed that such risk factors typically work proximally (e. g., positive consumption expectations) or distally (e. g., negative emotions) to influence substance use. In addition, characteristics of the broader cultural, socio-institutional, and immediate developmental contexts in which children and adolescents grow up (e. g., low social control or easy access to substances) can increase the risk for substance misuse (Petraitis et al., 1998). Moreover, protective factors that decrease the likelihood for adolescent substance misuse have been a focus of research (Silbereisen & Weichold, in press). Among such factors are positive relationships to parents or other adult role-models, external support systems (e. g., school), and positive attitudes towards school and learning (Jessor et al., 1998). The extent to which the potential influence of these factors can be generalized across different national, cultural or ethnic groups is not yet fully understood. Identifying differences in the balance of risk and protective factors among different groups may explain why adolescents from different countries differ in their substance-use behaviours. This article will summarise some such explanations. Adolescents are exposed to cultural traditions, social practices, and cultural norms which transact with developmental contexts. Across different cultures, pertinent influences on substance use vary, including patterns and methods of use, social acceptance, or policies on advertisement (Unger et al., 2004). For example, there may be cultural differences in the level or type of developmental resources provided or in the ease of access adolescents have to substances (e. g., laws against alcohol and tobacco advertisement, low consumption rate for general population, fines for smoking and drinking in public places). Another example relates to differences in access to organized and structured after-school activities, which are known to provide protection through positive role-modelling and social norms. Thus, some risk and protective factors may be culturally specific in their nature or importance. The investigation of differences in the role of risk and protective factors on adolescent substance misuse is of concern for health professionals aiming for theory-based development, implementation, and dissemination of effective prevention strategies. If risk and protective factors are similarly important for explaining substance use in different contexts, universal program components are appropriate for adolescents of different national or cultural groups (WHO, 1997). In the case of context-specific effects of risk and protective factors on substance use, culturally specific prevention components may be more adequate in meeting the target groups’ needs (Springer et al., 2004). Thus, cross-national research aiming at the comparison of the risks and protective factors related to substance misuse is necessary for recommending effective prevention strategies and social policies.