© 2018 Bentham Science Publishers. Thrombolytic therapy kick-started the era of modern cardiology but in the last few decades it has been largely supplanted by primary percutaneous coronary intervention (PCI) as the go-to treatment for acute myocardial infarction. However, these agents remain important for vast populations without access to primary PCI and acute ischemic stroke. More innovative uses have recently come up for the treatment of a variety of conditions. This article summarizes the history, evidence base and current use of thrombolytics in cardiovascular disease. © 2018 Bentham Science Publishers.