A variety of environmental and genetic factors modulating the risk for alcoholism have been described, which predominantly act by interacting with each other. For example, the family, peers and society determine the level of exposure to stress and alcohol, while genes modulate how sensitive an individual responds to both. The resulting behaviors feed back to the social environment, modulating and in the worst case increasing further stress exposure. We here review neurobiological evidence how such a process of mutual interaction can involve and affect drinking. In at-risk adolescents it may have been in force for many years before they have their first alcoholic drink, increasing their risk for addiction by generating allostatic load. As an example, psychiatric disorders involving attention deficit, hyperactivity, or disruptive behaviors first evolve during childhood and are influenced by all the above factors. They are also strongly associated with harmful adolescent drinking and later alcohol use disorders. One important implication of this concept is that issues such as family adversity, adolescent psychiatric disorders, or adolescent drinking might not only be associated with, but causally related to, the risk for later addiction. They are targets for preventive interventions, which should start as early as possible in subjects at-risk.