Patients with venous thromboembolism (VTE) are prone to the development of both short-term and long-term complications that can substantially affect their functional capacity and quality of life. Patients with deep vein thrombosis (DVT) often develop recurrent VTE or the post-thrombotic syndrome, whereas patients with pulmonary embolism (PE) can develop long-term symptoms and functional limitations along a broad spectrum extending to full-blown chronic thromboembolic pulmonary hypertension. Clinicians who care for patients showing severe clinical manifestations of DVT and PE are often faced with challenging decisions concerning whether and how to escalate to more aggressive treatments such as those involving the use of thrombolytic drugs. The purpose of this chapter is to provide guidance on how best to individualize care to these patients