This meta-analysis evaluated the relation between social support and depression in youth and compared the cumulative evidence for 2 theories that have been proposed to explain this association: the general benefits (GB; also known as main effects) and stress-buffering (SB) models. The study included 341 articles (19% unpublished) gathered through a search in PsycINFO, PsycARTICLES, ERIC, and ProQuest, and a hand search of 11 relevant journals. Using a random effects model, the overall effect size based on k = 341 studies and N = 273,149 participants was r = .26 (95% CI [.24, .28]), with robust support for the GB model and support for the SB model among medically ill youth. Stress-buffering analyses suggest that different stressful contexts may not allow youth to fully draw on the benefits of social support, and we propose value in seeking to better understand both stress-buffering (effects of social support are enhanced) and reverse stress-buffering (effects of social support are dampened) processes. Key findings regarding other moderators include a different pattern of effect sizes across various sources of support. In addition, gender differences were largely absent from this study, suggesting that social support may be a more critical resource for boys than is typically acknowledged. Results also demonstrated the importance of using instruments with adequate psychometric support, with careful consideration of methodological and conceptual issues. Building upon these collective findings, we provide recommendations for theory and practice, as well as recommendations for addressing limitations in the extant literature to guide future investigations.