Practicing interventional radiologists (IRs) are routinely faced with challenging decisions that pertain to the management of patients with acute deep vein thrombosis (DVT). In this article, we describe five questions that are commonly posed by interventionalists and discuss both the indirect published evidence as well as our own experience in dealing with these issues. Our aim is to address procedural and, perhaps more importantly, nonprocedural-related knowledge domains with which the IR physician is less familiar and are often not directly addressed by published data or evidence-based clinical practice guidelines. This discussion is meant to facilitate a stronger understanding of the published literature as it pertains to the justifiable indications for endovascular thrombolytic therapy, the optimal use of anticoagulant therapy, and the reasonable use of adjuncts such as inferior vena cava filters and elastic compression stockings. Our goal is to provide a framework for practicing IRs to help them make the best clinical decisions for their individual patients and, ultimately, achieve optimal DVT treatment outcomes.