In 1960, Barritt and Jordan performed the first randomized trial demonstrating the efficacy of anticoagulant therapy in the treatment of venous thromboembolism. Since then, important therapeutic advances have been made in the treatment of deep venous thrombosis and pulmonary embolism. This paper reviews the important clinical trials involving anticoagulant therapy and vena caval interruption. The studies are discussed from a historical perspective, and an attempt is made to analyze both the thought processes that prompted their design and the reasons why they changed practice.