Significant advances in technology and therapy have led to dramatic improvements in the survival of preterm babies over the last 2 decades. Similarly, improvements in surgical and cardiac intensive care techniques have increased the feasibility of supporting even very small babies to the point of surgical repair, leading some to adopt an approach of early and complete surgical repair in preterm infants, with the aim of minimizing potential preoperative morbidity associated with extended medical management or surgical palliation. (1,2) However, multiple diagnostic and therapeutic challenges complicate the care of premature infants. Major errors in echocardiography are more common in neonates weighing less than 2.5 kg, (3) and the ideal timing and type of surgical intervention in premature infants remains unknown. These problems are compounded by the need for critical care practices that optimize management of immature cardiopulmonary, gastrointestinal, and neurological systems. This review will summarize some of the recent advances in neonatal and perinatal medicine, which have the potential to contribute to improved management of preterm infants with critical cardiac disease.