Substance use often starts and possibly remains throughout the teenage years and has become a major public health concern. Tobacco, alcohol and drugs are related to a significant mortality and morbidity. It becomes essential to develop an heuristic and preventive perspective, based on the identification of vulnerability factors of substance use behavior. This article focuses on the role of psychopathology, psychosocial variables and personality attributes in adolescents' vulnerability to substance use. We analyse the recent literature and the main issues of a personal survey among French high school students. Further perspectives are discussed in terms of early therapeutic intervention and preventive of substance use. (C) 2001 Editions scientifiques et medicales Elsevier SAS.