The National Institutes of Health has established a clinical transplant research program focusing on translational research in kidney transplantation. The program has been developed with a multidisciplinary approach under a common administrative structure that integrates transplant physicians and surgeons with clinical laboratory and data analysis support personnel. The program has achieved excellent clinical outcomes despite focusing exclusively on investigational methods and serving a diverse and medically complex patient population. Novel approaches toward consenting, computer integration, and tissue acquisition have been layered over interventional and observational studies to serve the scientific mission while delivering quality transplant care.