The main cause of superior vena cava syndrome (SVCS) is malignant disease. However, multiple other diseases must be considered in the differential diagnosis and a new entity, SVCS due to central venous catheters, represents an etiology of increasing importance. SVCS due to malignancy should not be considered as a radiotherapeutic emergency. Careful management including invasive procedures such as mediastinoscopy to make a definite diagnosis should be performed when necessary by skilled practitioners, as specific therapy depends on a histologic diagnosis. Irradiation remains the standard treatment for many solid tumours, particularly non-small cell lung cancer. For chemosensitive tumours such as small cell bronchogenic carcinoma or lymphoma, chemotherapy can be recommended as initial treatment, and it is associated with high regression rates of the SVCS. In the case of a recent thrombosis of the superior vena cava, fibrinolytics may be applied as suggested by the experience obtained with central venous catheters.