Eliminating racial and ethnic health disparities requires restructuring the biomedical models that have focused on the individual as the level of analysis and emphasized the parts rather than the whole. A recently developed understanding of human physiology and adaptive regulation, constructs of allostasis and allostatic load, provides a theoretical orientation that needs to be explored. Thus, the purpose of this article is to present an orientation of allostasis and allostatic load as a theoretical framework for exploring health disparities. This article will (a) present a general background on the evolution of relevant physiologic theories, (b) offer the general theoretical definitions and explanations of allostasis, allostatic load, and mediation processes, (c) examine empirical evidence for the constructs, and (d) discuss the implications of this orientation for health disparities research.