This chapter demonstrates the role of the cardiovascular system as a contributor to the mechanisms of twin-to-twin transfusion syndrome (TTTS) and the essential role that cardiovascular characterization plays in diagnosing and monitoring the condition. It reviews the pathophysiology of TTTS and its impact on the cardiovascular system. The chapter discusses current methods for cardiovascular assessment, treatment strategies and the impact these have on the progression of cardiovascular disease and long-term implications. The longitudinal assessment of TTTS demonstrated that the circulatory derangement results in cardiac deterioration in a subset of patients. TTTS is believed to result from unidirectional flow across arteriovenous anastomoses within the shared placental mass with a paucity of bidirectional venovenous and arterioarterial anastomoses. The scoring system incorporates features unique to TTTS that quantify the cardiovascular burden of the disease. In TTTS, the twin pair is composed of the same genetic make-up suggesting that additional prenatal factors are involved.