Cardiovascular disease is a major cause of morbidity and mortality. Numerous risk scores exist to identify healthy individuals at increased risk of developing cardiovascular disease. Although platelets are a key mediator in the pathogenesis of cardiovascular disease, the role of platelet activity measurements and the incidence of cardiovascular disease are uncertain. Platelet aggregometry-the most well studied method of platelet function testing-is associated with risk factors for cardiovascular disease. However, data supporting platelet aggregation and incident cardiovascular disease is conflicting. Plasma markers of platelet activation are promising candidates. Soluble CD40L and P-selectin are easily measured with a standardized ELISA, and there is some data to suggest an association with cardiovascular disease, but further studies are required. While mean platelet volume is a promising candidate, platelet count and bleeding time are not specific for platelet activity nor are they associated with cardiovascular disease in a healthy population. For this field to progress, we recommend large-scale, prospective studies that measure a battery of these platelet function tests in individuals without cardiovascular disease to better understand the associations, if any, between platelet activity and cardiovascular disease.