In this article, we make the case that social epidemiology provides a useful framework to define the environment within gene-environment (G × E) research. We describe the environment in a multilevel, multidomain, longitudinal framework that accounts for upstream processes influencing health outcomes. We then illustrate the utility of this approach by describing how intermediate levels of social organization, such as neighborhoods or schools, are key environmental components of G × E research. We discuss different models of G × E research and encourage public health researchers to consider the value of including genetic information from their study participants. We also encourage researchers interested in G × E interplay to consider the merits of the social epidemiology model when defining the environment.