There is both a biological and environmental component to the neural substrates for various forms of psychopathology. Brain dysfunction itself not only constitutes a formidable liability to psychopathology, but also has an impact on environmental and social responses to the individual, compounding the risk for an adverse outcome. Environmental conditions, such as social and physical stimulus deprivation, poverty, traumatic stress, and prenatal drug exposure, can further compromise brain function in the context of existing liabilities. The relationship between genetic and environmental processes is interactive, fluid, and cumulative in their ability to influence an individual's developmental trajectory and alter subsequent behavioral outcomes. Given the codependent relationship between these processes, brain function is now believed to be malleable via manipulations of the environment in ways that may decrease liability for psychopathology. Research that explores these relationships and ways in which interventions can redirect this developmental track may substantially advance both the science and practice of prevention. Studies attempting to isolate the neurobiological effects of socioenvironmental factors are reviewed, implications for intervention strategies are discussed, and a future research agenda is proposed to provide greater insight into specific brain-environment relationships. Armed with this knowledge, prevention scientists may eventually design programs that directly target these effects to reverse or attenuate negative outcomes.