This article reviews different theoretical models concerning the prevention of substance use by adolescents. The models differ in their concepts and in their assumptions. Because the models describe different parts of the substance use problem, they can be combined to provide the basis for the design of information-based prevention programs. For example, in order to understand adolescent development, identity models or attachment models can be used. To understand adolescent norm changes, cultural models or peer system models can be applied. To understand how adolescents cope in specific situations where alcohol and other drugs are available, models that include concepts like self-esteem, drug expectations, existing norms, and perceived control of substance use can be employed. All preventive programs need to be pretested as well as evaluated both during and postprogram. The models mentioned may be used as frameworks in an evaluation, i.e., the variables and the assumptions in the models can be used as hypotheses to establish whether the desired results are achieved as a consequence of the selected strategies and techniques in the preventive program. A greater knowledge of the social and psychological processes preventing substance use will put us in a better position to influence and understand adolescent substance use in the future.