This article provides the reader with an overview and an update on antithrombotic stroke-prevention strategies. Relevant journals were hand-searched by the authors to compile a broad, but not comprehensive, summary of innovative and clinically relevant studies. These findings were then summarized to provide an expert opinion on selected fields of medical stroke prevention. We conclude that aspirin, clopidogrel or dipyridamol-aspirin are the cornerstone therapies in patients with noncardioembolic stroke. More potent antiplatelet drugs or the combination of aspirin and clopidogrel prevent more ischemic events but also lead to more bleeding complications. For secondary stroke prevention in patients with atrial fibrillation, oral anticoagulation is more effective than aspirin or the combination of aspirin and clopidogrel.