Type D personality, a synergy between negative affectivity and social inhibition, has established itself as a serious risk factor for morbidity and mortality in patients suffering from cardiovascular disease. In this review, we summarize studies on the validity of the assessment methods of Type D, emphasizing its role as an independent vulnerability factor in the progression of cardiovascular disease. We further present evidence on the physiological characteristics that accompany the 2 psychological traits negative affectivity and social inhibition and may mediate the relation between personality and prognosis in heart disease. Further research needs to determine the mechanisms by which Type D affects the course and outcome of cardiovascular disease as well as how Type D patients may benefit from psychosocial intervention.