Upper extremity deep venous thrombosis (UEDVT) makes up approximately 1-4% of all episodes of deep venous thrombosis (DVT). Risk factors for UEDVT include central venous catheterization, strenuous upper extremity exercise or anatomic abnormalities causing venous compression, inherited thrombophilia, and acquired hypercoagulable states including pregnancy, oral contraceptive use, and cancer. Unexplained or recurrent UEDVT should prompt a search for inherited hypercoagulable states or underlying malignancy. Clinical presentations include arm, neck, and shoulder pain; edema; skin discoloration; tenderness; and venous distension. Because UEDVT is frequently asymptomatic until complications ensue, a high index of suspicion is required for patients with one or more risk factors for thrombosis. Pulmonary embolism and post-thrombotic syndrome are the most common sequelae of UEDVT. Early detection and treatment of UEDVT decrease complications, morbidity, and mortality. Compressive ultrasonography is an effective and economical means of confirming the clinical diagnosis in most patients. Traditional anticoagulant therapy of UEDVT is giving way to a multimodal approach involving transcatheter thrombolytic therapy followed by a minimum of 3 months of warfarin sodium anticoagulant therapy, venous decompression as needed, and balloon angioplasty with stenting for treatment of residual stricture. Low-dose anticoagulant therapy can safely and effectively mitigate the increased risk of UEDVT associated with the use of central venous catheters.