Component-based approaches for cumulative risk assessment provide an important tool for informing public health policy. While current quantitative cumulative risk assessments focus narrowly on pesticides that share a mechanism of action, growing scientific evidence supports expansion of their application to encompass stressors that target a common disease. Case studies have demonstrated dose additive effects of chemicals with different mechanisms of action on liver steatosis, craniofacial malformations, and male reproductive tract developmental disruption. Evidence also suggests that nonchemical stressors such as noise or psychosocial stress can modify effects of chemicals. Focused research attention is required before nonchemical stressors can routinely be included in quantitative cumulative risk assessments.