Given the potency of modern immunosuppressive agents, kidney transplantation across alloantingen barriers is a routine phenomenon with excellent 1-year graft survival in most centers. However, the improvement in 1-year graft survival has not been matched by improvements in long-term graft function and chronic allograft nephropathy (CAN) remains the second commonest cause of graft attrition over time. Calcineurin inhibitors, namely cyclosporine A (CyA) and tacrolimus, have been implicated as causal agents in the development of the fibrotic processes that are the hallmarks of CAN. Many studies have, therefore, concentrated on the improvement of long term graft function through the modulation of immunosuppressive therapy. It is the purpose of this review to describe and appraise the available evidence for the prevention and management of CAN through modulation of immunosuppressive agents.