We introduce this supplemental issue of Prevention Science, which brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect heterogeneity. These studies follow two general paradigms: three papers report findings from single randomized preventive intervention trials, while the remaining papers develop and apply new methods for combining data from multiple studies to evaluate effect heterogeneity more broadly. Colleagues from NIMH and SAMHSA also provide commentaries on these studies. They conclude that synthesis of findings from multiple trials holds great promise for advancing the field, and progress will be accelerated if collaborative data sharing becomes the norm rather than the exception.Keywords Integrative data analysis . Adolescent depression . Randomized trials . Moderation Depression affects a substantial proportion of the population and results in significant distress, disability, and economic cost (Kessler et al. 2005). The risk for depression rises substantially during adolescence and young adulthood, with lifetime prevalence estimates for major depressive disorder reaching from 17% to as high as 40% of the population (Moffitt et al. 2010), and growing with each decade cohort. Over a third of all people who have one episode of major depression will have one or more recurrent episodes, leading to severe and chronic burden for many (Hardeveld et al. 2010). As a result, there has been a major effort over the past decade to develop and test programs to prevent depression. These programs have targeted adolescents based on the notion that early intervention may be able to reduce risk for initial onset, as well as short-circuit the cycle of recurrence.Randomized trials have provided evidence that many of these interventions are effective in reducing risk for subsequent depression. However, some trials also find that these interventions are not equally beneficial for all participants, and that initial benefits may change over time (Merry et al. 2011;Stice et al. 2009). This raises questions about preventive effect heterogeneity: that is, do different adolescents respond differently to preventive interventions? And if we find evidence of differential effects, what might account for it, and how might that help us shape the next generation of prevention programs? In addition, can such findings provide new insights for our theories of depression etiology?This supplemental issue of Prevention Science brings together a set of papers from leading investigators who have conducted trials testing whether intervention programs prevent adolescent depression. Using data from these trials, these papers explore a series of factors that might account for variation in intervention benefit, employing several novel methods for assessing effect he...