Up to 25% of adolescent girls experience an episode of major depression, at least twice the rate found with adolescent boys. In addition to reducing the suffering associated with depression, prevention efforts with this high-risk population have the potential to avert short- and long-term functional impairment, reduce the risk of associated mental and physical health problems, and provide mental health services to teens who may not otherwise receive help. The effectiveness of such programs depends upon the ability to reach at-risk girls and provide effective intervention, and to accomplish these goals in ways that are sustainable in community settings such as schools. This article discusses the advantages and drawbacks of several methods of delivering prevention programs for adolescent depression, and highlights strategies to enhance the effectiveness and sustainability of these programs. Lessons learned from the implementation of a universal prevention program for Grade 9 girls (Resourceful Adolescent Program-RAP; Shochet et al., 2001) are discussed, and practical recommendations are provided with regard to systems, program, implementation, and evaluation factors. Session-by-session details of RAP are highlighted, focusing on cognitive-behavioral and interpersonal therapy concepts and methods, adapted for use in a classroom setting.