During the last decade, advances in minimally invasive technologies have spurred a renaissance in the aggressive treatment of venous thromboembolism (VTE) using percutaneous techniques. In this article, we outline the relative risks and benefits of endovascular VTE therapies, highlight clinical situations in which the benefits of endovascular treatment are likely to outweigh its risks, and provide an update regarding the specific new modalities that may be applied to VTE. Pharmacomechanical thrombolysis represents the most promising currently available method to treat VTE. However, pending demonstration that it actually improves VTE outcomes in randomized trials with long-term follow-up, a highly individualized approach to patient selection is recommended. At present, highly compromised patients with pulmonary emboli (PE) in whom systemic thrombolytic therapy has failed or is contraindicated are reasonable candidates for catheter-based PE interventions. Adjunctive pharmacomechanical catheter-directed deep venous thrombosis (DVT) thrombolysis is best indicated for the first-line treatment of patients with phlegmasia cerulea dolens, acute inferior vena cava (IVC) occlusion, and acute iliofemoral DVT after careful clinical assessment and a balanced discussion with the patient. It is hoped that multidisciplinary clinical trials with involvement by both interventionalists and pulmonary physicians will validate these techniques in the near future.