This chapter examines Life Skills Training (LST), a school-based preventive intervention designed to prevent adolescent substance use and abuse. LST targets key etiologic factors as described in a conceptual framework derived from social learning theory and problem behavior theory. The LST program consists of three major components: (a) a personal competence component that teaches self-management skills, (b) a social competence component that teaches an array of social skills, and (c) a drug resistance component that teaches health-related content, resistance skills, and pro-health attitudes and norms. LST has been extensively tested in a series of randomized trials and found effective in preventing the use/misuse of tobacco, alcohol, marijuana, and other psychoactive drugs. Over 30 years of research shows that LST works with a wide range of students, cuts the use of psychoactive substances in half, and reduces other health-risk behaviors. Findings indicate that the program is effective when implemented under different delivery conditions, by different program providers, with different age groups, and with different populations. Follow-up studies have provide evidence of the long-term effectiveness of LST. Independent economic analysis indicates that LST produces cost