Thrombolytic agents may have clinically significant beneficial effects in cardiac arrest. The application of thrombolytic drugs in the setting of current and antecedent cardiopulmonary resuscitation is well documented; however, it has not been systematically studied nor has it been widely considered. We provide a literature review of thrombolytic agents and cardiopulmonary resuscitation to discuss the need for randomized controlled trials and the possibility of benefits in acute resuscitation.