Alcohol, tobacco, and other drug use are important problems that typically begin during adolescence. Fortunately, substantial progress has been made in developing effective drug abuse prevention programs for youth over the past two decades. Prevention approaches that focus on the risk and protective factors associated with drug use initiation and those that teach skills related to social resistance are most effective. The Life Skills Training (LST) program is an effective primary prevention program for adolescent drug abuse that focuses on these factors as well as enhancing social and personal competence skills. This paper provides an overview of the theoretical underpinnings of the LST program, along with a description of the program's components, materials, and methods. Findings from over two decades of evaluation research are reviewed and demonstrate that the LST approach consistently produces positive behavioral effects on alcohol, tobacco, and other drug use. The role of competence enhancement-based primary prevention programs in preventing other negative behaviors during adolescence is discussed.