The pathogenesis of chronic renal allograft dysfunction was reviewed. Chronic rejection/chronic renal allograft nephropathy is the most prevalent cause of renal graft loss after the first year post-transplant. Both immunologic and non-immunologic factors play key roles in the pathogenesis of chronic allograft nephropathy. Acute rejection episodes are the most prevalent risk factor for chronic rejection. Many risk factors for chronic allograft nephropathy have been identified, such as glomerular hyper-filtration, delayed graft function, repeated acute rejection, systemic hypertension and hyperlipidemia. However, the precise pathogenesis of chronic allograft nephropathy remains obscure. The differential diagnosis of immunologically mediated chronic rejection and chronic allograft dysfunction caused by non-immunologic factors is usually impossible using clinical parameters. The histopathologic findings of chronic allograft nephropathy are progressive interstitial fibrosis with tubular atrophy and thickening of vascular intima, and these findings are non-specific. Therefore, the term chronic allograft nephropathy may be clinically preferable to chronic rejection to describe the gradual decline in graft function. The most effective way to prevent chronic allograft dysfunction is to avoid any kind of graft damage via immunologic or non-immunologic pathway.