Awareness and recognition of anatomic anomalies of the great vessels of the neck and chest are important for the interventional nephrologist, as central venous catheter placement is a common procedure. A persistent left superior vena cava (PLSVC) is the most common thoracic venous anomaly (0.3-0.5% of the population), and can present difficulty during internal jugular or subclavian vein catheter insertion, as well as pose a diagnostic dilemma. In this report, two cases of PLSVC are described, and the clinical significance and diagnosis of PLSVC are reviewed.