Steroid-resistant rejection after pediatric renal transplantation forms a rare but severe complication with a guarded prognosis particularly if this occurs late after transplantation. There is a paucity of data on how to manage these challenging rejection episodes, particularly in the pediatric literature. Mohan Shenoy et al. published a case series of 15 patients who were treated with anti-thymocyte globulin for steroid-resistant acute allograft rejection over a 15-year period in a single center in this issue of Pediatric Nephrology. While the results for the early rejection group were encouraging, the results in the eight patients with late rejection episodes after transplantation were unfavorable and afflicted with a high incidence of side-effects. Important diagnostic tools such as C4d staining of the renal transplant biopsy and the measurement of donor-specific antibodies were underutilized. The editorial reviews the importance of the differentiation between humoral and cellular rejection and the challenges of treating late antibody-mediated acute rejection in these patients. A multi-center approach is required to establish a registry of these events and ideally prospective randomized interventions should be designed to provide some evidence base for the management of this challenging complication after pediatric renal transplantation.