Atherothrombotic pathology represents a major health problem and its prevention may be considered a primary, relevant objective in the conditions considered at risk for cerebrovascular, cardiac, and systemic ischemic diseases. Patients with previous manifestations of this disease are in fact considered at high risk of recurrence as events concerning other vascular territories are involved. Long-term antiplatelet therapy with noncompetitive inhibitors of ADP-induced platelet aggregation such as clopidogrel demonstrates the efficacy of this therapeutic approach in different strategies of secondary prevention in patients at high risk of atherothrombotic manifestations. The opportunity to combine the efficacy and safety of drugs with different mechanisms of action on platelet aggregation such as aspirin and clopidogrel is under investigation and preliminary results are very promising.