Histological assessment of allograft biopsies is still the gold standard for typing and grading renal allograft rejection episodes. The technology employed for biopsy assessment and the resulting diagnostic classification did however not always keep pace with the rapidly evolving knowledge about the immunological mechanisms of rejection. As accurate recognition of these mechanisms is crucial for specific therapy and reliable risk assessment, it is mandatory to constantly adjust our diagnostic standards to current immunological knowledge. The introduction of antibody-mediated rejection as a diagnostic category a few years ago exemplifies the importance of defining renal allograft rejection according to the prevailing immunological mechanism. Current challenges are the diagnostic implementation of novel concepts like sub-clinical rejection or accommodation of grafts. This requires a reassessment of current diagnostic standards and likely also the development of new diagnostic tools. This article reviews novel concepts arising from studies on protocol biopsies and experimental models with specific focus on the potential and limitations of current diagnostic procedures for the detection and classification of recently appreciated conditions like sub-clinical rejection, accommodation and C4d-negative antibody-mediated rejection.