Between 40 and 90 cardiopulmonary resuscitations are performed per 100,000 inhabitants each year in western industrialised nations. In 50-70% of these patients, either fulminant pulmonary embolism or acute myocardial infarction is the underlying cause of cardiac arrest. Based on this fact, thrombolysis may represent a new and effective causal therapeutic strategy in patients suffering from cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. In the past, thrombolysis was contraindicated during cardiopulmonary resuscitation due to great fears of severe bleeding complications (resuscitation-mediated or lysis-induced intracerebral bleeding). For a long time, only clinical case reports or small clinical case series were reported in the literature, however, recently, the first clinical studies focusing on the safety and efficacy of thrombolytic therapy during out-of-hospital cardiopulmonary resuscitation have been published. Besides a specific therapeutic causal effect on pulmonary artery emboli and coronary artery thrombosis, experimental data strongly indicate that thrombolysis might also have an impact on cerebral microcirculatory reperfusion during and after cardiopulmonary resuscitation. This effect might be responsible for the exceptionally good neurological outcome observed in patients treated with thrombolytic agents during cardiopulmonary resuscitation and might be a result of the proven imbalance of the endogenous coagulation system in patients suffering from cardiac arrest. This coagulation imbalance is thought to be responsible for postresuscitation cerebral microcirculatory reperfusion disorders in patients after cardiac arrest and cardiopulmonary resuscitation. In summary, recent clinical and experimental data focusing on thrombolysis during cardiopulmonary resuscitation strongly indicate, that thrombolysis may represent a new and relatively safe therapeutic option during resuscitation after cardiac arrest due to acute myocardial infarction or fulminant pulmonary embolism. If the results of an international randomised, controlled clinical multicentre trial presently underway confirm the previous clinical findings, thrombolysis during cardiopulmonary resuscitation could become an important part of future cardiopulmonary resuscitation algorithms.