Thrombolysis has become standard treatment in the great majority of patients with an acute transmural myocardial infarction. Large placebo-controlled trials have shown that thrombolytic therapy, when given within 6 hours after onset of symptoms, reduces infarct size, preserves left ventricular function and improves survival. Because of discrepancies observed between the effects of thrombolysis on left ventricular function and survival and since beneficial effects have also been observed in subgroups of patients treated after 6 hours, additional mechanisms of actions (besides salvage of ischemic myocardium) have been supposed: limitation of infarct expansion and left ventricular remodeling, increased electrical stability and provision of collaterals to other myocardial regions. The equal clinical outcome with different agents, in spite of proven differences in efficacy for early recanalization, in GISSI-2/International and ISIS-3 has further challenged the importance of the original pathophysiological mechanism (early reperfusion and myocardial salvage). The results of recent megatrials (GUSTO, EMERAS and LATE) and of a recent meta-analysis (FTT's collaborative Study Group) have resolved many uncertainties. The implications of these recent trials for the selection of both patients and thrombolytic strategies and for the future development of new treatment can not be overestimated.