In vitro studies indicate that kidney transplantation from gene-edited pigs in which expression of all three of the known glycan xenoantigens has been deleted may be more challenging in nonhuman primates (NHPs) than it will be in human recipients. Furthermore, pig-to-human xenotransplantation offers several other advantages - (i) the patient can communicate with the surgical team; (ii) recipient microbiological monitoring and environment will be clinical-grade; and (iii) sophisticated graft monitoring and imaging techniques, (v) therapeutic interventions, e.g., dialysis, plasmapheresis, and (v) intensive care can be deployed that are not easily available in NHP laboratory models. We suggest, therefore, that progress to develop safe, informative human clinical trials will be accelerated if pilot clinical cases are initiated. The selection of patients for kidney xenotransplantation can include those who are at high risk of dying imminently, e.g., those experiencing increasing vascular access challenges with no realistic alternative therapy available, and those who have been accepted onto the waitlist for an allograft, but who are unlikely ever to receive one. Patients with an increased risk of dying include those with (i) age >60 years, (ii) blood groups O or B, and (iii) diabetic nephropathy. UNOS data indicate that an average of 25 patients on the kidney waitlist in the USA die or are removed from the list every day (i.e., >9,000 each year). Given the improved xenograft survival observed in preclinical studies, we suggest that it is time to plan a small pilot clinical trial for healthy dialysis patients who understand the risks and potential benefits of kidney xenotransplantation.