The 2009 Institute of Medicine report on prevention of mental, emotional, and behavioral disorders (National Research Council & Institute of Medicine, 2009b) presented evidence that major depression can be prevented. In this article, we highlight the implications of the report for public policy and research. Randomized controlled trials have shown that the incidence of major depressive episodes can be significantly reduced. Meta-analyses suggest that 22% to 38% of major depressive episodes could be prevented with currently available methods. We argue that if major depressive episodes can be prevented, the health care system should provide routine access to evidence-based depression prevention interventions, just as it provides inoculations for other common and debilitating health problems. At the same time, researchers should pursue the major directions advocated by the Institute of Medicine report to increase the enduring effectiveness of future prevention interventions. These directions include taking a developmental perspective, learning to identify groups at high risk, and testing evidence-based interventions that are likely to have the widest reach. Scientific evidence has shown that clinical depression can be averted. Our societies must take action to reduce clinical depression to the lowest possible level. This article is one of three in a special section (see also Biglan, Flay, Embry, & Sandler, 2012; Yoshikawa, Aber, & Beardslee, 2012) representing an elaboration on a theme for prevention science developed by the 2009 report of the National Research Council and Institute of Medicine.