BACKGROUND: Superior vena cava syndrome in hemodialysis patients resulting from previous or current use of a tunneled central vein catheter is a rare but potentially severe condition. Two aspects have to be addressed during management and treatment: the restoration of central venous flow and the creation of an alternative vascular access to guarantee hemodialysis. RESEARCH DESIGN: Conforming to the current guidelines and literature, we present a stepwise approach and discuss therapeutic options. The removal of the tunneled central vein catheter should be attempted and a native vascular access created whenever feasible. RESULTS: First, an upper extremity AVF should be preserved or, as in our case, made functional. Endovascular treatment of CVSO should primarily consist of balloon dilatation. Placement of a stent or stent graft should be considered as a secondary option. HeRO graft placement may be considered in recurrent CVSO and recanalization with a Surfacer. LL-AVF or AVG need to be discussed and may be an alternative for certain HD patients when the risk of lower limb ischemia and infection is considered. CONCLUSION: Several therapeutic options are available and the basic principles are well established in the literature, although the level of evidence is not high. Therefore, we propose a stepwise and interdisciplinary approach to guide the challenging decision-making process in SVC.