Analgesic nephropathy has long been considered a potentially preventable cause of renal disease. Early reports were described in patients who consumed analgesics containing phenacetin. In recent data, the removal of phenacetin from analgesic preparations resulted in a reduction in analgesic-induced end stage renal disease in Europe and Australia. However, a reduction in the incidence of analgesic nephropathy has not occurred uniformly, suggesting that phenacetin is not the sole cause. Current data raise concerns regarding adverse renal effects of acetaminophen and nonsteroidal antiinflammatory drugs. Aspirin taken alone may be of least concern. The diagnosis of analgesic nephropathy is suggested in subjects with chronic renal failure, a history of daily consumption of analgesic preparations, small bumpy kidneys, and renal papillary necrosis or chronic interstitial nephritis. However, the spectrum of disease may be changing, because these agents also may increase the risk of cardiovascular disease and chronic renal disease due to nephrosclerosis, glomerulonephritis, and diabetes mellitus. Potential pathogenetic mechanisms in analgesic nephropathy include direct cellular injury induced by analgesics, prostaglandin inhibition with reduction or redistribution of renal blood flow, and interesting new concepts regarding the role of caffeine in increasing oxygen demand and reducing oxygen supply in the medulla. The primary goal of therapy is discontinuation of analgesic consumption. Because of the association between analgesic intake and uroepithelial tumors, surveillance of patients for neoplasm is suggested.