With the established benefits of living-donor kidney transplantation, our primary emphasis at Mayo Clinic, Rochester has been to develop protocols that allow living donation to occur even in the presence of relatively unusual or generally contraindicated situations. This approach has significantly increased the number of patients receiving kidney transplants in the past few years. Our protocols for extended criteria donors and recipients along with the exclusive use of laparoscopic donor nephrectomy have been major contributors to the increase in volume. ABO-incompatible and positive-crossmatch living-donor kidney transplant protocols also have increased the availability of transplants for our patients. Protocol biopsies have aided in the diagnosis of subclinical rejection, polyoma virus and chronic allograft nephropathy. Innovative immunosuppressive protocols such as calcineurin inhibitor-free immunosuppression have decreased rejection and improved both short and long-term renal allograft survival.