The prevalence of cardiovascular disease is one of the major causes of overall mortality. It kills almost 18-19 million individuals annually. There are a number of synthetic drug departures but the major effects are hemorrhagic impact, immunogenicity, and high price, due to restricted applications. Actinomycetes are the most economically and biotechnologically valuable prokaryotes. They are known to be responsible for the production and successful exploitation as a source of secondary metabolites, and are found to be abundant and active in marine sediments. Natural thrombolytic drugs are increasingly reported as safer, more fascinating and less costly. Actinokinase is a serine protease which cleaves α-chain, β-chains and γ-chains of fibrinogen. Hence, such mechanistic property makes actinokinase an interesting feature. These microbial fibrinolytic proteases are used for therapeutic approach of medical interest and have biotechnological applications to treat cardiovascular diseases. © 2015 Bentham Science Publishers.