Diabetes mellitus is an independent predictor of adverse outcomes including mortality in patients presenting with STEMI and with the use of thrombolytic treatment, this has significantly come down. ST-segment elevation myocardial infarction (STEMI) is caused by complete occlusion of a major epicardial coronary artery and is usually trigged by rupture of vulnerable plaque, with formation of fibrin-rich occlusive thrombus. Fast restoration of myocardial blood flow is the main stay in the treatment of STEMI, in order to restrict the infarct size and improve the outcome. This chapter covers the streptokinase, alteplase, reteplase, and tenecteplase. Tenecteplase (TNK-tPA) is produced by recombinant DNA technology using Chinese hamster ovary cells. Reteplase (r-PA) is a second-generation lytic agent and is a mutant of alteplase.