The GUSTO trial and an Australian consensus meeting in 1993 led to the recommendation that recombinant tissue plasminogen activator (r-TPA) was the preferred thrombolytic in patients with acute myocardial infarction (AMI) and ST segment elevation under the age of 75, whose infarction was anterior, who could be treated within four hours of the onset of symptoms and who did not have a contraindication to thrombolysis. Available data suggest that streptokinase (SK) should not be administered in a patient who has received this drug three days or more previously. New data on the risks of stroke confirm that the use of r-TPA is associated with a higher risk of intracranial haemorrhage than SK, and those with a high risk profile for intracranial haemorrhage (hypertension and advanced age) should receive SK rather than r-TPA. It may be justified to give r-TPA to any patient with a large infarct regardless of location, within four hours of the onset of infarction in an attempt to achieve TIMI flow grade 3 (complete) reperfusion, reduce mortality and improve left ventricular function and clinical outcomes. The focus for the future will be on how to treat more patients earlier with thrombolytic agents, rather than the choice of agent.