Cardiovascular disease (CVD) is highly prevalent and is associated with tremendous morbidity and mortality. In the United States, nearly 62,000,000 people have some form of CVD, including hypertension, coronary heart disease, stroke, congestive heart failure and congenital cardiovascular defects. CVD is the number one cause of death in the United States, claiming more than 950,000 lives in 1999 (American Heart Association, 2001). The most common form of CVD is hypertension, which affects 50,000,000 Americans. While chest pain is a common accompaniment of CVD, only relatively recently have disturbances of pain perception in CVD become a topic of significant scientific interest. Over the past 25 years, interactions between the cardiovascular and somatosensory systems have become increasingly recognized, and considerable research has identified important effects of cardiovascular responses on pain perception. This chapter will summarize the literature regarding the relationship of cardiovascular factors with pain perception. First, the influence of several cardiovascular variables on pain perception will be reviewed, including resting blood pressure, parental history of hypertension, and cardiovascular reactivity. Then, potential mechanisms underlying these associations will be discussed. Next, research examining pain perception in various cardiovascular disorders will be presented, and the chapter will conclude with a discussion of clinical implications and directions for future research.