Summary The challenge facing the transplant team is how to rapidly and efficiently identify transplantable organs from affected donors and allocate them to suitable recipients likely to benefit most from such organs. It has been suggested that careful selection of recipients could mitigate adverse outcomes resulting from poor prognostic factors in the donor. 148–150 Selection of donors and recipients to reduce non-immunerelated injury can be facilitated by age-matching donors and recipients, avoiding transplants from higher-risk older donors into high-risk recipients (retransplant or high panel-reactive antibody), performing dual transplants into one recipient, 151–154 and considering kidneys from older donors with the absence of hypertension and a high estimated creatinine clearance (≥80 mL/min) to be suitable for transplantation into a younger recipient. It is most likely that rejection (T-cell-mediated and alloantibody-mediated) and nonimmunologic factors work in concert to increase stress on the transplanted kidneys. There has been a body of work suggesting that nonimmunologic factors exert their effects by triggering rejection. In fact, nonimmunologic factors probably have their effects by governing the extent of injury and the ability of limiting cells in the graft to repair and survive rather than by triggering rejection. Little is known about the rules governing homeostasis and the response to injury in the human renal epithelium. The same statements can be made about the renal arterial system; we know little about why arteries develop FIT with age and hypertension. What cell is limiting? Is fibrosis primary or secondary to limitations in other cells such as endothelium? It is for this reason that we have emphasized the importance of the emerging area of limitations on somatic cells. The customer wants renal function (ie, functioning somatic cells). We need to understand more of the rules governing the survival of these cells in the injuries and stresses of the transplant—rejection and nonimmunologic stresses. Organ survival involves multiple sciences; the sciences of cellular senescence, epitheliology, and vascular biology should join with immunology in the important challenges and opportunities for progress in transplantation.