Approximately 960 babies are born per year in the United States with hypoplastic left heart syndrome. Over the last 20 years, advances in surgical techniques, perioperative care, cardiopulmonary bypass, and intensive care unit management have converted this previously fatal condition to one with a neonatal survival rate of 90% to 92% for standard risk patients. Understanding the factors affecting the balance of pulmonary blood flow and systemic blood flow and ensuring adequate cardiac output and end-organ perfusion is critical to successful outcomes. Extracorporeal membrane oxygenation remains an important support modality following stage I palliation. This chapter discusses this syndrome and describes treatment options.