The antiplatelet drugs, commonly used in the prevention and treatment of cerebrovascular disease, possess a number of effects that are independent of direct antiplatelet actions. Beneficial and detrimental effects both occur. The endothelium is an important mediator of these non-antiplatelet effects. We performed a literature search to locate articles related to acetylsalicylic acid (aspirin), clopidogrel, ticlopidine, and dipyridamole and the interactions of these medications with the endothelium. The role of each of the above medications is explored in relation to vasodilation, inflammation, oxidation, platelet-leukocyte interactions, and thrombogenic tendency via platelet-vessel wall interactions.