Cardiovascular diseases, like coronary heart disease or artery disorders (arteriosclerosis, including artery solidification), heart failure (myocardial infarction), arrhythmias, congestive heart condition, stroke, elevated vital signs (hypertension), rheumatic heart disorder, and other circulatory system dysfunctions are the most common causes of death worldwide. Cardiovascular disorders are treated with stenting, coronary bypass surgery grafting, anticoagulants, antiplatelet agents, and other pharmacological and surgical procedures; however, these have limitations due to their adverse effects. Fibrinolytic agents degrade fibrin through enzymatic and biochemical processes. There are various enzymes that are currently used as a treatment for CVDs, like streptokinase, nattokinase, staphylokinase, urokinase, etc. These enzymes are derived from various sources, like bacteria, fungi, algae, marine organisms, plants, snakes, and other organisms. This review deals with the fibrinolytic enzymes, their mechanisms, sources, and their therapeutic potential. © 2022 Elsevier B.V., All rights reserved.