Background: In approaches to health promotion in adolescents, unhealthy behaviors are no longer regarded as independent processes, but as interrelated. This article presents a systematic literature review of school-based interventions targeting multiple adolescent behaviors simultaneously. Methods: A systematic literature search was performed using PubMed, Science Direct, and PsychInfo. Only papers written in English and describing original research were included. Results: Of 33 papers included, 23 focused on quantitative behavioral changes, and 10 on the evaluation of intervention development, implementation, and/or institutionalization. Parental and community involvement in the intervention seemed to be positively associated with effective changes in student health behaviors, whereas creating a healthy school environment and/or policies were less strongly associated with intervention effectiveness. Findings indicated that, for adequate implementation, an intervention should be integrated in pre-existent school settings, fine-tuned to its target population or environment, involve family and the community, and be led by the school itself, with there being a "healthy school coordinator" to coordinate the program. Conclusion: A multi-behavior, multi-actor approach would appear to be the most effective way to promote, at school, healthy behaviors among adolescents. (Contains 4 tables and 1 figure.)