While substance misuse among adolescents is globally on the increase, prevention remains the main approach. This paper highlights some relevant clinical issues of recent interest. It provides some aspects which could help in the clinical assessment of referred adolescents and how these differ from adults. It is suggested that unlike adult addicts who mainly use psychoactive substances just to feel normal, adolescents use psychoactive substances in many different contexts. The 5 different clinical contexts of involvement based on drug use context include exploratory or experimental; social; emotional or instrumental, habitual, and dependent or addictive. Suggestions in relation to clinical managements and treatment approaches, including individual counseling, family therapy, group therapy, and external support networks are presented. In conclusion, the case for setting up specialist services for adolescents who misuse psychoactive substances is made.