Superior vena cava (SVC) syndrome is a historic entity that is reemerging as an important, albeit still uncommon, contemporary vascular disease condition. The causes of SVC syndrome have evolved dramatically over the last century: whereas the majority of originally described cases were due to infection, contemporary presentations are now predominantly associated with the presence of an intravascular device and/or mediastinal malignancy. Multiple underlying pathologic mechanisms often coexist to confer risk for SVC syndrome. Although the diagnosis is still best made at the bedside, advanced imaging modalities may be used to clarify etiology, grade severity, and facilitate intervention. Treatment of SVC syndrome often requires a combination of noninvasive and invasive therapies. With regard to invasive strategies, endovascular approaches to revascularization are now considered first-line given their relative safety and efficacy. Fortunately, both endovascular and open surgical interventions can offer definitive therapy in a majority of cases.