Emerging evidence suggests that psychosocial stress and toxicants may interact to modify health risks. Stress-toxicant interactions could be important in chemical risk assessment, but these interactions are poorly understood and additional research is necessary to advance their application. Environmental health research can increase knowledge of these interactions by exploring hypotheses on allostatic load, which measures the cumulative impacts of stress across multiple physiological pathways, using knowledge about physiological pathways for stress-related health effects, and evidence of common target pathways for both stress and toxicants. In this article, critical physiological pathways for stress-related health effects are discussed, with specific attention to allostatic load and stress-toxicant interactions, concluding with research suggestions for potential applications of such research in chemical risk assessment.