Current immunosuppressive protocols have significantly decreased graft loss to acute rejection but have had no effect on graft loss to chronic rejection. Recently, attention has been focused on the prevention and management of chronic rejection. Centers must come to a uniform definition of this phenomenon so that studies can be compared. It is believed that the definition should include both a typical clinical course and a definitive biopsy. For kidney transplant recipients, the major risk factor for the development of chronic rejection appears to be a previous acute rejection episode. Other important risk factors include low-dose maintenance immunosuppression and previous infection. Noncompliance probably plays a role in some patients. For extrarenal transplant recipients, chronic rejection has been associated with cytomegalovirus infection and/or HLA-DR matching. Immunoregulatory processes posttransplant may modify or attenuate the development of chronic rejection. Large, prospective clinical studies are required to further elucidate risk factors and to determine the effect of intervention.