Superior vena cava syndrome is today primarily a disease associated with malignancy. Thrombosis of the superior vena cava associated with the use of intravascular devices or extraluminal obstruction from malignancy is now recognized as an important pathophysiologic process in the syndrome. Irradiation has long been the mainstay of treatment. Newer treatments include more effective chemotherapy for certain cancers such as lymphoma and small-cell carcinoma, fibrinolytics to treat thrombosis, and interventional radiologic techniques. Expandable metallic stents have been shown to improve the quality of life for patients who, in the past, quickly succumbed to the disease process. Current management stresses the importance of accurate diagnosis of the underlying etiology before treatment. Only under extreme emergent conditions such as laryngeal or cerebral edema should irradiation proceed without a diagnosis. Future studies should address the role of anticoagulant therapy and the timing of interventional techniques in relation to radiation or chemotherapy.