During the past two decades, several advances have resulted in marked improvement in medium-term survival for infants and children undergoing heart transplantation. Unfortunately, progress has been less dramatic in the field of lung and heart-lung transplantation, where there is little evidence of improved outcomes. The procedures remain palliative and all transplant recipients are at risk for the adverse effects of non-specific immunosuppression, including infections, lymphoproliferative disorders, and non-lymphoid malignancies. In addition, current immunosuppressive agents have narrow therapeutic windows and exhibit a wide array of organ toxicities, posing special challenges for the young patient who must endure life-long immunosuppression. New immunosuppressive regimens have lowered the rates of acute rejection but appear to have had relatively little impact on the incidence of chronic rejection, the principal cause of late graft loss. The ultimate goal is to induce a state of donor-specific tolerance, wherein the recipient will accept the allograft indefinitely without the need for long-term immunosuppression. This quest is currently being realised in animal models of solid organ transplantation, and offers great hope for children undergoing heart and lung transplantation in the future.