Aspirin's benefit in preventing vascular outcomes is well established. It reduces the relative risk for stroke, myocardial infarction, and vascular death by about 25% compared with placebo. Almost 10 years ago we learned that ticlopidine is more effective than aspirin (about 12% relative risk reduction for stroke or death). However, ticlopidine has important adverse effects. In 1996, the Clopidogrel versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial showed that clopidogrel, a new thienopyridine similar to ticlopidine, is also more effective than aspirin (by a similar amount) and is as safe as aspirin. Also in 1996, the European Stroke Prevention Study 2 (ESPS-2) showed that dipyridamole alone prevents stroke and that when combined with aspirin it is more effective, probably comparable to ticlopidine and clopidogrel. Dipyridamole combined with aspirin reduced the relative risk for stroke or death by about 13% compared with aspirin alone. Both clopidogrel and dipyridamole are safe but will cost more than aspirin. Aspirin also appears beneficial for acute stroke treatment. The Chinese Acute Stroke Trial (CAST) and the International Stroke Trial (IST) demonstrated that aspirin given at the time of an acute ischemic stroke reduces the risk for early death (about 5 less/1,000 treated), recurrence or death (about 10 less/1,000 treated), and dependence (about 5 less/1,000 treated). Overall, the benefits of aspirin in acute stroke treatment and stroke prevention are definite but modest. Combination therapy with antiplatelet agents that act through different mechanisms is a promising way to maximize the benefits of antiplatelet treatment.