The immunohistochemical detection of the complement degradation product C4d in renal allograft biopsies has gained considerable clinical interest in recent years. The accumulation of C4d along peritubular capillaries is generally regarded as a marker for an antibody-mediated allo-response and is associated with poor graft survival. The aim of this review is to discuss histological findings associated with the deposition of C4d. Emphasis is placed on diagnostic and therapeutic implications. Unanswered questions regarding C4d and graft injury are highlighted.