Currently, most prevention efforts are framed as universal interventions. However, despite the demonstrated efficacy of many prevention programs, variability in response is the rule with some participants responding very little and others accounting for the bulk of the positive impact of the program. Better understanding the processes associated with better and worse response to prevention is a critical first step in refining and adapting existing programs, or alternatively designing new prevention programs with enhanced outcomes. Because vulnerabilities to substance use, emotional problems, risky sexual behavior and other behavioral problems are influenced by a combination of environmental, genetic, and epigenetic factors, mediated in part through psychological processes (Kreek et al., 2005; Rutter et al., 2006), the study of genetic and epigenetic vulnerability and susceptibility factors provides an important starting point for efforts to address this critical need. A growing body of research on differential genetic susceptibility indicates that efforts to enhance prevention impact may benefit from consideration of the contribution of individualgenetic differences to treatment response (Brody et al., 2013). In addition, the recent expansion of genetic research to include a focus on epigenetic change provides considerable promise for the development of indicated prevention and individually tailored prevention efforts. However, before this promise can be realized, a number of theoretical and practical challenges remain. Thus, through this special section, we provide a foundation for a new era of prevention research in which the principles of prevention science are combined with genomic science. In the current special section we bring together authors to deal with genetic and epigenetically driven processes relevant to depression, substance abuse, and sexual risk taking. Together they comment on, and provide data relevant to, assessment, research and statistical methods, The papers help to inform the development of a new generation of prevention programs that go beyond universal programs and sensitively target key processes while providing greater precision regarding prediction of population-level impact.