Renal transplant recipients now enjoy excellent short term graft survival. However, modern immunosuppression protocols have not led to proportional improvements in long term outcome. When progressive allograft dysfunction develops, clinical signs and symptoms are frequently not specific enough to pin point the underlying etiology. A biopsy is an extremely useful tool to distinguish between immunologic causes of graft dysfunction (chronic rejection) and non-immunologic causes such as chronic calcineurin inhibitor toxicity, recurrent disease, glomerulonephritis, obstructive uropathy, and renal artery stenosis. In recent years, antibody mediated injury and chronic BK virus nephropathy have become recognized as significant players in the pathogenesis of so-called chronic allograft nephropathy. Histopathologic examination can also quantify the degree of chronic injury, which can assist in the decision to list patients for re-transplantation.