The major diagnoses carried by children undergoing cardiac transplantation worldwide are congenital heart defects, cardiomyopathies, and retransplantation. The leading diagnosis in infancy is congenital heart disease, whereas cardiomyopathy predominates in older children. In view of this wide spectrum of diagnoses, the perioperative management of these children requires medical, interventional, and surgical expertise in treatment of complex congenital heart defects, end-stage heart failure, and cardiac transplantation. According to the Pediatric Heart Transplantation Survey database, the majority of children listed for cardiac transplantation eventually require higher levels of cardiac support before transplantation. The team caring for these children should be prepared to escalate support in a timely fashion in order to avoid end-organ dysfunction or a catastrophic event that will remove the patient from the cardiac transplantation list. The first step is advanced hemodynamic monitoring in a specialized pediatric cardiac intensive care unit and initiation of inotropic support. Further escalation of care should be based on careful analysis of the hemodynamic profile, end-organ function, and biochemical markers of perfusion and myocardial stress. A patient who continues to deteriorate in spite of inotropic support requires positive pressure ventilation, and if deterioration continues, mechanical circulatory support is initiated. Cardiac transplantation is a challenging operation, and even more so in children with complex congenital heart defects. The abnormal cardiovascular anatomy requires planning and anticipation of possible pitfalls as hypoplasia of the aortic arch, abnormal pulmonary arteries, and abnormal systemic and pulmonary venous connections. The time required to remove adhesions in children with prior cardiac operations increases the ischemic time of the graft and the risk of primary graft dysfunction. Assessment of pulmonary vascular resistance in children with congenital heart defects is problematic, and even children with a normal transpulmonary gradient and pulmonary vascular resistance are at increased risk of postoperative pulmonary hypertension and right ventricular graft failure. The postoperative course is directly linked to the patient's preoperative physical condition and perioperative course. The induction of immunosuppression and the use of plasmapheresis in children with a positive cross-match may lead to further hemodynamic compromise. If severe primary graft dysfunction evolves, early initiation of extracorporeal membranous oxygenator is indicated to avoid irreversible end-organ dysfunction.