There is a growing awareness of the role of oral pathogens in cardiovascular disease. Chronic oral disease such as periodontitis, leads to inflammation and bleeding of the gums. This bleeding provides a viable portal of entry for the bacteria to the circulation. Once in the circulation oral bacteria can interact with circulating platelets. Their ability to support platelet adhesion and induce platelet aggregation are critical steps in the pathogenesis of the infective process. Oral bacteria use multiple mechanisms to interact with, and activate platelets thus contributing to cardiovascular disease. This chapter will review the various mechanisms oral bacteria use to interact with platelets.