Pediatric end-stage renal disease (ESRD) requires renal replacement therapy by either dialysis or kidney transplantation. This chapter focuses on the unique medical and surgical care of the pediatric transplant patients. The etiology of ESRD has an important impact on the preparation of the patient for transplantation, postoperative management, and overall graft survival. Vascular thrombosis of the renal graft is a devastating event seen in about 2-3% of pediatric renal transplants and is a major cause of graft failure in the first year following transplant. Definitive diagnosis of graft rejection requires a graft biopsy for histologic and immunohistochemical evaluation in addition to other appropriate investigations to exclude other causes of rise in serum creatinine. Chronic allograft nephropathy (CAN) is the most common cause of eventual graft failure in the pediatric transplant population, comprising about 35% of all causes of graft failure.