Apart from traditional risk factors, psychosocial characteristics are increasingly considered as potential predictors of cardiovascular disease (CVD). The concept of stress is relevant when discussing the relationship between psychosocial factors and CVD. Among stress types and definitions (ie, marital stress, work stress), "perceived stress" presents a global and comprehensive stress construct and is based on the concept that individuals actively interact with their environment, appraising potentially threatening or challenging events in the light of available coping resources. However, the role of perceived stress in CVD incidence has not yet been completely elucidated. Thus, we evaluate perceived stress as a CVD risk factor by reviewing the literature. We also discuss the relationship between negative affect and CVD development.