Among both immune and nonimmune factors implicated in the pathogenesis of chronic renal allograft rejection, acute rejection episodes represent a strong and consistent predictor. However, all acute rejection episodes are not equally predictive of chronic renal allograft rejection. Early and mild acute rejection episodes do not usually cause chronic renal allograft rejection. On the other hand, late and severe acute rejection episodes occurring more than one year after transplantation are particularly strong predictors of chronic renal allograft rejection. The number of HLA mismatches is a risk factor, but its influence may not be independent of acute rejection and other risk factors. Proteinuria and recently hypoalbuminemia are also independent risk factors for chronic renal allograft rejection. However, whether these nonimmune factors are merely the result of chronic renal allograft rejection, or whether they contribute to the pathogenesis of renal injury in chronic renal allograft rejection is yet unclear. Better HLA matching, new strategies to decrease the severity of acute rejection, and measures to prevent late acute rejection, as well as prospective evaluation of the therapies to reduce proteinuria and other nonimmune risk factors for chronic renal allograft rejection are needed.