Summary Functional genomics strategies have been slow to penetrate research on human stress and coping, but recent conceptual advances have yielded a raft of new findings relating social and psychological conditions to broad alterations in human gene expression. This article reviews the field of human stress genomics, analyzes some of the conceptual and technical issues that initially hampered its progress, and outlines an abstractionist approach to genomic data analysis that has revealed a surprisingly consistent pattern of human transcriptional responses to diverse types of socio-environmental adversity. This field is now poised for another round of significant advances as research begins to incorporate the effects of DNA polymorphism, target a broader array of healthy and diseased tissues, and identify general teleologic and regulatory themes by pooling results over a growing body of studies analyzing the human transcriptional response to stress.