Protocol biopsies in renal transplantation are those that are procured at predetermined times post renal transplantation, regardless of renal function. These biopsies have been useful to study the natural history of the transplanted kidney as they have detected unexpected - i.e. "subclinical" pathology. The most significant subclinical pathologies that have been detected with protocol biopsies have been acute lesions, such as cellular and antibody mediated rejection, and chronic lesions, such as interstitial fibrosis and tubular atrophy, and transplant glomerulopathy. The potential benefit of early recognition of the above lesions is that their early treatment may result in improved long-term outcomes. Conversely, the identification of normal histology on a protocol biopsy, may inform us about the safety of reduction in overall immunosuppression. Our centre, as well as others, is attempting to develop non-invasive methods of immune monitoring of renal transplant patients. However, we believe that until such methods have been developed and validated, the protocol biopsy will remain an indispensable tool for the complete care of renal transplant patients.