Thrombosis, the blockage of blood vessels with clots, can lead to acute myocardial infarction and ischemic stroke, both leading causes of death. Other than surgical interventions to remove or by pass the blockage, or the generation of collateral vessels to provide a new blood supply, the only treatment available is the administration of thrombolytic agents to dissolve the blood clot. This article describes a comprehensive review of streptokinase (SK). We discuss the biochemistry and molecular biology of SK, describing the mechanism of action, structures, confirmational properties, immunogenecity, chemical modification, and cloning and expression. The production and physico-chemical properties of this SK are also discussed. In this review, considering the properties and characteristics of SK that make it the drug of choice for thrombolytic therapy.