The superior vena cava (SVC) syndrome is usually associated with advanced malignancy and has a dismal prognosis. In order to analyze the impact of newer diagnostic and therapeutic modalities, we retrospectively examined the last 45 consecutive cases of SVC syndrome treated over a 12-year period. The underlying causes were advanced lung cancer (57%), mediastinal tumors (20%), and metastatic solid malignancy (5%). Forty-two patients (93%) were treated with external beam radiotherapy and/or chemotherapy with a mean patient survival of 3 months; 11 of 42 patients (26%) were treated without histologic diagnosis. Symptoms of SVC obstruction resolved in 80% of patients who underwent radiotherapy, with a mean interval of 4 weeks. The most common cause of death was respiratory arrest. Of the three patients with benign disease, two underwent caval reconstruction with greater than 3-year patency and relief of symptoms. We conclude that (1) SVC syndrome portends a grim prognosis when associated with malignancy but usually responds to radiation or chemotherapy; (2) CT scan is the best available method to document the extent and location of involvement; and (3) patients with benign disease should be evaluated for caval reconstruction, which may produce rewarding long-term results.