Adolescence is a tumultuous period in the lifetime of an individual confronted to major changes in emotional, social and cognitive appraisal. During this period of questioning and doubt, while the executive functions are still maturing, the abstract reasoning remains vague and the response inhibition loose; ultimately the adolescent scarcely resists temptation. Consequently, adolescence is often associated with uninhibited risk-taking, reckless behaviours, among which are alcohol and illicit drugs use. Here, we discuss how the development of the prefrontal cortex (which critically contributes to rational decision-making and temporal processing of complex events) can be associated with the idiosyncratic adolescent behaviour, and potentially uncontrolled alcohol use. Most importantly, we present clinical and preclinical evidence supporting that ethanol exposure has deleterious effects on the adolescent developing brain. Ultimately, we discuss why a late maturing prefrontal cortex represents a ripe candidate to environmental influences that contribute to shape the adolescent brain but, potentially, can also trigger lifelong maladaptive responses, including increased vulnerability to develop substance use disorder later in life.