Antiplatelet therapy is a mainstay of secondary prevention of ischemic strokes. Recent studies, such as Prevention Regimen for Effectively Avoiding Second Strokes (PRoFESS), the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial, and the European/Australasian Stroke Prevention in Reversible Ischaemia Trial (ESPRIT), have added much to our understanding about how best to utilize the various antiplatelet agents available. Aspirin has been shown to reduce the risk of recurrent strokes, and the combination of aspirin and dipyridamole has repeatedly been shown to outperform aspirin alone. Recently, clopidogrel was demonstrated to be "noninferior" to an aspirin/dipyridamole combination, and can be considered as a first-line agent. The American Stroke Association and American Heart Association have clear recommendations on how to utilize these agents.