Hypoplastic left heart syndrome is a rare but serious form of congenital cardiac disease, characterized by underdevelopment of the components of the left heart, rendering the left ventricle non-functional. Its aetiology is largely unknown, but there is certainly a genetic component. Prenatal diagnosis nowadays uncovers about half of cases. Postnatal options for treatment include comfort care, 3-stage palliative surgery, or cardiac transplantation. In this review, we discuss the morphology, possible pathogenetic mechanisms, clinical management, and perspectives of prenatal intervention based on work in animal models.