Sudden cardiac death is a leading cause of death in Europe. In the vast majority, myocardial infarction or pulmonary embolism is the underlying cause. Lethality is still high, especially if the arrest occurs out of hospital. For these two severe conditions, thrombolysis has proven to be an established therapy. Coronary perfusion is restored or the occlusion in the pulmonary arteries is removed, restoring normal circulation and normalising right-ventricular afterload. Nevertheless, thrombolysis was contraindicated during cardio-pulmonary resuscitation (CPR) for many years due to the fear of severe bleeding complications. Case reports and series using thrombolysis as successful ultima ratio therapy during prolonged CPR were soon followed by retrospective and interventional studies. These trials showed significantly improved survival for patients after thrombolysis during CPR. Nevertheless, none of these trials was randomised. Other trials showed that bleeding complications do not occur more frequently after thrombolysis during CPR. Experimental investigations demonstrated that thrombolysis during CPR improves cerebral microcirculation. The results of the randomised, multicenter trial TROICA show that tenecteplase alone, does not significantly improve survival. Further studies on thrombolysis during CPR with additional administration of heparin and acetylsalicylic acid must follow to ascertain the role of thrombolysis during CPR. Although thrombolysis during CPR is not a standard therapy, it should not be withheld from patients in whom pulmonary embolism is the suspected cause of cardiac arrest, as well as in selected other patients on the physician's individual decision according to recent guidelines.