It is now possible to identify hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is considerable uncertainty, however, as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio (INR) of 2 to 3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by the risk of major bleeding and the inconvenience associated with oral vitamin K antagonists. Although low-intensity anticoagulation at a target INR of 1.5 to 2 has recently been shown to be effective in preventing recurrent venous thromboembolism after 3 to 6 months of treatment at an INR of 2 to 3, it has not been demonstrated to reduce the risk of major bleeding complications. A decision as to the overall benefit of extended anticoagulation therefore continues to require clinical assessment of an individual patient's risk of recurrence in the absence of treatment and the risk of bleeding at the chosen INR target range.