The aim of this systematic review is to describe and evaluate the effects of interventions used for preventing or reducing substance use among adolescents under 18 years of age. Studies (N = 27) available in CINAHL and PubMed from 2007 to 2010 were included. Results showed that family-based interventions and combined interventions have significant outcomes for substance use among adolescents. Similarly, school-based interventions were effective in providing knowledge about substance use, which eventually reduced the substance use. Further research should be conducted in different cultures as well as on computer-based interventions targeting both genders. (Contains 1 table and 1 figure.)