Anticoagulation with unfractionated heparin and low molecular weight heparin have been the mainstay in the management of acute pulmonary embolism with or without deep vein thrombosis. This approach to care has evolved based on the severity of pulmonary embolism and the need to rapidly restore pulmonary blood flow. This was followed by thrombolytic therapies both systemic and catheter directed, all of which improved care. The use of catheter devices evolved with the addition of ultrasound and suction thrombectomy devices. All the above mechanical approaches were either preceded and/or followed by concomitant use of unfractionated heparin or low molecular weight heparin. The latest addition to management has been use of the direct oral anticoagulants. These agents are used following interventions for massive and intermediate risk pulmonary emboli and are continued to prevent recurrent disease. Warfarin continues to be used for extended management in special populations. This chapter will review unfractionated heparin, low molecular weight heparins, warfarin, and direct oral anticoagulants in the management of pulmonary embolism.