Several personality characteristics have been linked in multiple well-designed prospective studies to subsequent physical health outcomes, such as longevity and the development and course of cardiovascular disease. The evidence is strongest for negative affectivity/neuroticism, anger/hostility and related traits, and optimism. Models of mechanisms underlying these associations have emphasized physiological effects of stress, exposure to stressors, and health behavior. Preliminary evidence supports the viability of some mechanisms, but formal mediational tests are lacking. In addition to addressing limitations and inconsistencies in this literature, future research should address developmental aspects of these psychosocial risk factors, contextual moderators of their health effects, and intervention applications in the prevention and management of disease. In these efforts, greater incorporation of concepts and methods in the structural, social-cognitive, and interpersonal perspectives in the field of personality are needed.