Unplugged is a school-based prevention programme designed and tested in the EU-Dap trial. The programme consists of 12 units delivered by class teachers to adolescents 12–14 years old. It is a strongly interactive programme including a training of personal and social skills with a specific focus on normative beliefs. The aim of this work is to define the theoretical model of the program, the contribution of the theories to the units, and the targeted mediators. The programme integrates several theories: Social Learning, Social Norms, Health Belief, theory of Reasoned Action-Attitude, and Problem Behaviour theory. Every theory contributes to the development of the units’ contents, with specific weights. Knowledge, risk perception, attitudes towards drugs, normative beliefs, critical and creative thinking, relationship skills, communication skills, assertiveness, refusal skills, ability to manage emotions and to cope with stress, empathy, problem solving and decision making skills are the targeted mediators of the program.