Chronic rejection results from recurrent episodes of subclinical or clinically evident acute rejection, with or without involvement of chronic rejection-specific allogeneic immune mechanisms. The tissue damage occurs over a prolonged period of time, which allows the emergence of antigen-independent tissue repair mechanisms and intrarenal adaptations in response to progressive loss of renal mass (Fig. 1). The combination of these mechanisms leads, very likely, to the tissue remodeling of chronic rejection. The heterogeneous expression of chronic rejection may result from different types and specificities of allogeneic immune reactions as well as different contributions of antigen-independent factors that modulate the antigen-dependent tissue responses to injury. The extent to which these mechanisms participate in the overall picture is presently unknown as immunological parameters are not measured routinely in the follow-up of patients with chronic graft dysfunction. Furthermore, some grafts may undergo tissue remodeling as a consequence of predominantly antigen-independent mechanisms. Therefore, the term chronic allograft dysfunction may clinically be preferable over chronic rejection to describe the gradual decline in graft function months or years after transplantation in the absence of a well-defined mechanism or an accepted treatment.