The aim of thrombolytic therapy in acute myocardial infarction is the early, complete and sustained restoration of bloodflow in the infarct-related artery. In a randomized trial in 421 patients with acute myocardial infarction front-loaded rt-PA (100 mg in 90 min) showed a significantly higher 90-min patency (84.4%) in comparison with APSAC (70.3%). In-hospital mortality was significantly lower after rt-PA (2.4%) versus 8.1% after APSAC. While a single bolus injection of rt-PA produced lower patency and higher reocclusion rates, double bolus injections showed more promising results (90 min patency > 70%). A new recombinant plasminogen activator BM 06.022 (r-PA) with a longer half life can be given as a single bolus injection. In a dose-finding study r-PA produced rapid thrombolysis with a 90-min patency of 66% (10 MU) and 76% (15 MU). There was no excess in re-occlusions or bleeding complications. Although these results are quite promising, the search for the ideal thrombolytic strategy is still ongoing.