Vascular endothelial injury associated with arterial narrowing leads to platelet adhesion and aggregation at the site of endothelial injury and to the local accumulation of several mediators that promote platelet aggregation and vasoconstriction, including thromboxane A2, serotonin, adenosine diphosphate, platelet activating factor, oxygen-derived free radicals, activated thrombin, and tissue factor. At the same sites of endothelial injury, there is a reduction in absolute or relative amounts of the endogenous inhibitors of platelet aggregation and vasoconstriction, including prostacyclin, endothelium-derived relaxing factor (nitric oxide), and tissue plasminogen activator; the loss of the effects of the endogenous inhibitors preventing platelet aggregation and vasoconstriction helps to create a prothrombotic and vasoconstrictive environment. Endothelial injury occurs as a result of atherosclerotic plaque fissuring or ulceration, flow shear stress, hypertension, diabetes mellitus, immune complex deposition, infection, and mechanical injury in the form of diagnostic and therapeutic catheterization. Endothelial injury and the accumulation of platelet- and other cell-derived mediators promotes neointimal proliferation in an exaggerated wound-healing response, resulting in further anatomic narrowing of artery in the subsequent days and weeks. Future methods that may prove useful in protecting the individual with these vascular problems from acute myocardial infarction and its consequences are inhibition of multiple mediators of platelet aggregation and vasoconstriction, restoration of the presence of the normal endogenous inhibitors of platelet aggregation and vasoconstriction, and/or rapid therapeutic regeneration of the injured endothelium.