Calcineurin inhibitors, cyclosporine and tacrolimus, have improved allograft survival in solid organ transplantation. Indeed, they have reduced the incidence of acute rejection episodes of cadaveric allograft recipients. Although marked progression has been made in initial survival rates, long-term kidney graft survival has yet to show such encouraging results. Chronic allograft dysfunction is the major hindrance to long-term graft survival and many components contribute to this entity, both immunologic and nonimmunologic. Chronic calcineurin nephrotoxicity is a major factor in chronic allograft dysfunction. This review will highlight the current understanding and management of calcineurin nephrotoxicity in kidney transplantation.