Equity and social well-being considerations make Black–White health disparities an area of important concern. Although previous research suggests that discrimination- and poverty-related stressors play a role in African American health outcomes, the mechanisms are unclear. Allostatic load is a concept that can be employed to demonstrate how environmental stressors, including psychosocial ones, may lead to a cumulative physiological toll on the body. We discuss both the usefulness of this framework for understanding how discrimination can lead to worse health among African Americans, and the challenges for conceptualizing biological risk with existing data and methods. We also contrast allostatic load with theories of historical trauma such as posttraumatic slavery syndrome. Finally, we offer our suggestions for future interdisciplinary research on health disparities.