Early and late kidney graft survival has improved considerably due to advances in clinical care, particularly immunosuppression. Many of the kidney transplants functioning today should serve their new owners for their life expectancy. What challenges this viewpoint and the main cause of late kidney function deterioration remains allograft nephropathy. Often this reflects an influence of the immunosuppression. Subclinical rejection, chronic nephrotoxicity, recurrent disease, infections, or diabetes may also contribute to this process. Optimal early and late immunosuppression is required, which provides efficacy without attendent risk for graft dysfunction due to nephrotoxicity. Since 1-year serum creatinine level often provides an indication of long-term graft function, early evaluation of subtle degrees of graft dysfunction should prompt a graft biopsy to identify treatable causes.