Venous thromboembolism is a frequently occurring and potentially fatal disease characterized by short-term and long-term sequelae. Conventional treatment consists of heparin and vitamin K antagonists, but there is an ongoing controversy if more aggressive therapy, such as thrombolytic drugs, should be used in selected patients to achieve faster clot lysis in pursuit of better clinical outcome. A review of the literature shows that thrombolytic therapy is not recommended in the treatment of venous thrombosis. Although in deep vein thrombosis systemically administered and catheter-directed thrombolysis both offer advantages in improving vein patency and reducing the postthrombotic syndrome (PTS), prevention of severe PTS remains unproved while the bleeding risk is high. In pulmonary embolism (PE), thrombolytic therapy is generally recommended for patients with massive PE and hemodynamic instability, despite scarce and inconclusive evidence. There is no evidence that thrombolysis has a benefit over standard anticoagulant treatment in normotensive patients with acute PE, but more research is needed to better identify the subgroup of patients with nonmassive PE in whom the risk-benefit ratio is most favorable. Until this group is defined and the benefit of thrombolytic therapy is demonstrated, thrombolytic therapy should only be considered in patients with signs of massive PE and hemodynamic shock.