The rapidly moving study of Gene-Environment interaction (G-E) needs interim conceptual tools to track progress, integrate findings, and apply this knowledge to preventive intervention. We define two closely related concepts: the social mediation of the expression of genetic influences and the interaction between the entire genotype and the social environment (G-E). G-E, the primary focus of this report, assesses individual differences in the full genotype using twin, sibling, and adoption designs and, for the most part, employs fine-grained analyses of relational processes in the social environment. In comparison, studies of Allele Environment interaction assess the influence on development of one or more measured polymorphisms as modified by environmental factors. G-E studies build on work showing how the social environment responds to genetic influences and how genetic influences shape the social environment. Recent G-E research has yielded new insight into variations in the sensitivity of the social environment to genotypic influences and provides clues to the specificity and timing of these environmental responses that can be leveraged to inform preventive interventions aimed at reducing genetic risk for problem behavior.