In this article, we explore current thinking and practices around the logics of difference in gene–environment interaction research in the post-genomic era. We find that scientists conducting gene–environment interaction research continue to invoke well-worn notions of racial difference and diversity, but use them strategically to try to examine other kinds of etiologically significant differences among populations. Scientists do this by seeing populations not as inherently homogeneous or heterogeneous, but rather by actively working to produce homogeneity along some dimensions and heterogeneity along others in their study populations. Thus we argue that homogeneity and heterogeneity are situational properties – properties that scientists seek to achieve in their study populations, the available data, and other aspects of the research situation they are confronting, and then leverage to advance post-genomic science. Pointing to the situatedness of homogeneity and heterogeneity in gene–environment interaction research underscores the work that these properties do and the contingencies that shape decisions about research procedures. Through a focus on the situational production of homogeneity and heterogeneity more broadly, we find that gene–environment interaction research attempts to shift the logic of difference from solely racial terms as explanatory ends unto themselves, to racial and other dimensions of difference that may be important clues to the causes of complex diseases.