Thrombolytic therapy reduces the mortality rate in patients with acute myocardial infarction. However, thrombolytic agents, which are primarily directed toward the lysis of fibrin, fail to achieve reperfusion in at least 20% of patients and an early reocclusion occurs in up to 25% of cases. The role of platelets in both thrombus resistance to lysis and early reocclusion is demonstrated by experimental and clinical observations. Platelets and the fibrinolytic system interact in numerous ways. Platelet activation can potentiate or inhibit the fibrinolytic process. The activation of the fibrinolytic system has been found to induce either an activation or an inhibition of platelet function. In animal models it has been shown that platelet-rich thrombi are resistant to lysis, and that platelets and fibrin still accumulate on lysing thrombi during effective thrombolysis. One of the most attractive strategies to optimize thrombolytic therapy is adjunctive treatment with pharmacological agents which inhibit platelet function.