Lower extremity deep venous thrombosis (DVT) has traditionally been divided into proximal and distal DVT. Proximal DVT is further subdivided into iliofemoral DVT, involving the common femoral vein and/or iliac vein, and represents an obstructive disease process with a worse prognosis than proximal DVT without involvement of these large draining veins. The anatomical reasons will be explored, and the data supporting these findings will be examined. Because iliofemoral DVT portends a worse prognosis in patients with lower extremity DVT, the risk-benefit profile is altered compared with proximal DVT without involvement of the common femoral or iliac draining veins. The initial anticoagulation management and catheter-based, invasive therapies currently available for treatment of iliofemoral DVT will be described, and the data supporting these techniques will be examined. (Prog Cardiovasc Dis 2011;54:70-76) (C) 2011 Elsevier Inc. All rights reserved.