Forty decades of sociological stress research offer five major findings. First, when stressors (negative events, chronic strains, and traumas) are measured comprehensively, their damaging impacts on physical and mental health are substantial. Second, differential exposure to stressful experiences is a primary way that gender, racial-ethnic, marital status, and social class inequalities in physical and mental health are produced. Third, minority group members are additionally harmed by discrimination stress. Fourth, stressors proliferate over the life course and across generations, widening health gaps between advantaged and disadvantaged group members. Fifth, the impacts of stressors on health and well-being are reduced when persons have high levels of mastery, self-esteem, and/or social support. With respect to policy, to help individuals cope with adversity, tried and true coping and support interventions should be more widely disseminated and employed. To address health inequalities, the structural conditions that put people at risk of stressors should be a focus of programs and policies at macro and meso levels of intervention. Programs and policies also should target children who are at lifetime risk of ill health and distress due to exposure to poverty and stressful family circumstances.