With improvements in short-term renal transplant survival, concerns regarding the long-term outcome are becoming more important. Chronic rejection is the single most important cause of graft failure in the first posttransplant decade, but its pathophysiology remains poorly understood. It has been suggested that chronic rejection is the tissue remodelling that is initiated by smoldering foci of inflammation initiated by acute rejection episodes, perhaps in conjunction with chronic rejection-specific allogeneic immune reaction. The chronicity of these processes leads to concurrent activation of tissue repair mechanisms and changes in renal hemodynamics, which contribute to the tissue remodelling that is characteristic for chronic rejection.