Of 207 pediatric patients who underwent orthotopic heart transplantation at Loma Linda University Medical Center through January 1993, 96% of infants under 6 months of age and 45% of older infants and children had complex structural heart disease. Twelve patients had visceral heterotaxia, 10 had isolated dextrocardia, and 16 had unusual atrial situs, including five with situs inversus. Therefore a prerequisite for successful heart transplantation in early life is a surgical team skilled in the management of congenital heart disease. Transplantation in very early life is usually primary therapy, whereas in older infants and children it is an exercise in reoperative and reconstructive heart surgery. The keys to operative success include the following: (1) Appropriate recipient selection; (2) en bloc recovery of all veins and arteries required for anatomic reconstruction; (3) adequate myocardial protection; and (4) use of low-flow hypothermic perfusion and intermittent circulatory arrest as required. Although there is wide variability in the anatomic presentation of many potential recipients with congenital heart disease, only two absolute anatomic contraindications have been identified. Absence or marked hypoplasia of central pulmonary arteries and absence or markedly diminutive pulmonary veins are two anatomic variants that do not yield to heart transplantation therapy. Previous palliative surgery, variations of atrial situs, anomalies of pulmonary or systemic venous connections, and great vessel malformations all create challenge for the surgical team and potential risk for the recipient, but none preclude operative success.