Although frequently considered synonymous with acute tubular necrosis, acute renal failure may be brought about by primary disease in any of the four histologic components of the kidney: glomerular, tubular, interstitial, or vascular. It is reasonable to ask whether our current classification system of renal pathology and descriptive approach to renal biopsy interpretation in this setting is optimal. Assessment of renal transplant biopsies performed in the setting of acute dysfunction is becoming much more quantitative, therapy-oriented, pathogenesis-based, and standardized. It would be highly beneficial to the field if similar changes occurred in the approach to native kidney biopsies in acute renal failure. Tighter linkage should be established between promising new developments in the research laboratory and the clinical practice of renal pathology with creation of therapy-oriented classifications which employ standardized quantitative lesion assessment. In a field largely limited to traditional empirical therapies, new pathogenesis-oriented therapeutic approaches to native kidney acute renal failure and allied conditions should be developed based on the products of enlightened renal pathology research.