The central role of platelets in the pathophysiology of arterial vascular disease has focused attention on the development of effective platelet inhibitor modalities to mitigate the clinical consequences of atherothrombotic disease. Aspirin has been the gold standard of therapy and is effective in cerebral, coronary and peripheral arterial disease with a 25% reduction in myocardial infarction, stroke and vascular death. The platelet ADP receptor antagonists were developed to further improve the clinical results of therapy. Ticlopidine provides an additional 10% relative risk reduction over aspirin alone in stroke prevention and coronary stent placement. However, ticlopidine is accompanied by occasional life-threatening adverse hematological events. The action of clopidogrel is similar to that of ticlopidine, and it is comparably effective. However, the side-effect profile of clopidogrel is much more favorable.