Any substance which prevents blood from clotting or prolongs the clotting time is called an anticoagulant. Some of them are isolated from natural sources like heparin, hirudin, anti-thrombin, urokinase, and streptokinase and some are synthetic e.g., Warfarin, acenocoumarol, brodifacoum. Several proteins with anticoagulant properties isolated from natural sources are currently employed in treating thrombotic disorders. Heparin and Warfarin are the two most widely used natural and synthetic anticoagulant drugs respectively, for the treatment of thrombotic disorders like deep vein thrombosis, acute myocardial infarction, thromboembolism, prevention of systemic embolism in patients with atrial fibrillation. This review article focuses on currently available and newer classes of natural and synthetic anticoagulants, their mechanism of action, and therapeutic potential. Pubmed databases was used for articles selection, papers on natural and synthetic anticoagulants were obtained and reviewed. This review article helps in better understanding the underlying pathways of currently available natural and synthetic anticoagulants and will be useful in designing/discovering new classes of drugs.