Despite the significant reduction in mortality, ischemic stroke is the leading cause of morbidity and mortality in adults in industrialized countries. Antiplatelet therapy has reduced the risk of stroke and other vascular events. Although most commonly used treatment is aspirin, other antiplatelet drugs with different mechanisms of action have been developed. Clopidogrel blocks platelet aggregation by inhibiting the adenosine diphosphate receptor and the subsequent activation of the complex IIb/IIIa. In addition to its antiplatelet action, it also has pleiotropic effects, reducing the inflammatory mechanisms that occur during ischemia. Clopidogrel has demonstrated a benefit over aspirin in preventing vascular events, especially in patients at high cardiovascular risk. In this paper we review the main studies that have been conducted with clopidogrel in preventing ischemic stroke, either as monotherapy or in combination with other antiplatelet agents.