Randomized controlled trials have shown that patients with venous thromboembolism benefit from a minimum of three months of anticoagulant therapy. After this period, it was suggested that patients with an expected annual recurrence rate of < 5% could safely discontinue treatment. Using a population-based approach for stratification, these patients are those with major transient risk factors, and represent the minority. For all other patients, including those with previous episodes of venous thromboembolism, cancer, or unprovoked events, this treatment duration may not be sufficiently protective. Because extending anticoagulation for additional three to nine months does not result in further, long-term reduction of recurrences, indefinite treatment duration should be considered. However, case-fatality rate for major bleeding in patients taking warfarin for more than three months is higher than case-fatality rate of recurrent venous thromboembolism. Thus, an individual patient approach to improve and increase the identification of those who can safely discontinue treatment at three months becomes necessary. Clinical prediction rules or management strategies based on D-dimer levels or residual vein thrombosis have been proposed and need further refinement and validation. Specific bleeding scores are lacking. Meanwhile, the oral direct inhibitors have been proposed as potential alternatives to the vitamin K antagonists, and aspirin may provide some benefit in selected patients who discontinue anticoagulation. Deep vein thrombosis in unusual sites is associated with less, but potentially more severe recurrences, in particular in patients with splanchnic vein thrombosis who also face an increased risk of bleeding complications while on treatment.