Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in the United States and worldwide. In this review, we examine the scientific evidence in support of current dietary recommendations to increase fruit and vegetable intake for CVD prevention. Available evidence indicates that persons who consume more fruits and vegetables often have lower prevalence of important risk factors for CVD, including hypertension, obesity, and type 2 diabetes mellitus. Recent large, prospective studies also show a direct inverse association between fruit and vegetable intake and the development of CVD incidents such as coronary heart disease and stroke. However, the biologic mechanisms whereby fruits and vegetables may exert their effects are not entirely clear and are likely to be multiple. Many nutrients and phytochemicals in fruits and vegetables, including fiber, potassium, and folate, could be independently or jointly responsible for the apparent reduction in CVD risk. Functional aspects of fruits and vegetables, such as their low dietary glycemic load and energy density, may also play a significant role. Although it is important to continue our quest for mechanistic insights, given the great potential for benefits already known, greater efforts and resources are needed to support dietary changes that encourage increased fruit and vegetable intake.