Deep vein thrombosis (DVT) is the most common form of venous thromboembolism and can result in significant morbidity, including postthrombotic syndrome (PTS) in up to 50% of patients. Randomized trials of catheter-directed thrombolysis (CDL) have demonstrated that patients with symptomatic iliofemoral DVT (IFDVT) are at the greatest risk of developing PTS, and that CDL has a limited ability to prevent PTS. Consequently, various new trials and technologies to prevent PTS are being assessed. Novel technologies have opened new opportunities for treatment. For example, results from the prospective, multicenter CLOUT registry have shown effective treatment of thrombus of all ages and low PTS rates at 2-year follow-up using mechanical thrombectomy with the ClotTriever System (Inari Medical, Irvine, CA). The Protrieve sheath (Inari Medical) includes an expandable funnel that can trap emboli in the inferior vena cava (IVC) in cases involving bilateral proximal disease or thrombosed IVC filters, and the RevCore catheter (Inari Medical) is the first mechanical thrombectomy device designed specifically to address stent thrombosis. Aspiration thrombectomy techniques, such as computer-assisted vacuum thrombectomy (Indigo System, Penumbra, Alameda, CA) and volume-controlled aspiration mechanical thrombectomy (FlowTriever System, Inari Medical), are also increasingly used in the contemporary treatment of IFDVT. Combined mechanical and aspiration approaches (Aspirex System, BD, Franklin Lakes, NJ) are being investigated as well. Local treatment with anti-inflammatory drugs after recanalization (Bullfrog Micro-Infusion Device, Mercator MedSystems, San Leandro, CA) is being studied to determine its effect on preventing rethrombosis and disease symptoms. Data from ongoing registries and randomized controlled trials, including the BOLT, DEFIANCE, and REVIT studies, will continue to inform the treatment of patients with IFDVT.