The history of antithrombotic therapy is traced over the past 5 decades, with a focus on the treatment of 2 major disorders: venous thromboembolism and acute myocardial infarction. Five subjects pertinent to clinical management decisions are discussed: (1) theories of thrombosis and coagulation, (2) tests of coagulation, (3) the availability of therapeutic interventions, (4) techniques for the diagnosis of vascular obstruction, and (5) the use and misuse of clinical trials.