Persistent left superior vena cava (PLSVC) is the most common venous anomaly of the thorax affecting 0.5–2% of the general population. PLSVC with absent right SVC, which is also referred to as isolated PLSVC, occurs in 0.09–0.13% of patients. PLSVC should be suspected whenever a dilated coronary sinus is discovered on transthoracic echocardiography. Transthoracic echocardiography serves as an excellent modality to diagnose PLSVC. The presence of PLSVC can be confirmed by performing a bilateral “bubble study” with injection of agitated saline from both the left and the right peripheral arm veins. Although PLSVC is a benign condition, it may have important clinical implications in certain situations. We describe a case of PLSVC with an absent right SVC followed by a review of the literature and the clinical implications associated with this condition.