Rapidly accruing evidence from a diversity of disciplines supports the hypothesis that psychosocial factors are related to morbidity and mortality due to cardiovascular diseases. We review relevant literature on (a) negative emotional states, including depression, anger and hostility, and anxiety; (b) chronic and acute psychosocial stressors; and (c) social ties, social support, and social conflict. All three of these psychosocial domains have been significantly associated with increased risk of cardiovascular morbidity and mortality. We also discuss critical pathophysiological mechanisms and pathways that likely operate in a synergistic and integrative way to promote atherogenesis and related clinical manifestations. We conclude by discussing some of the important challenges and opportunities for future investigations.