Renal papillary necrosis (RPN) is a significant problem in human beings, especially in England and in Australia where it has been reported to account for 15% to 20% of patients needing renal transplants. Many compounds, including aspirin, phenacetin, phenylbutazone, indomethacin, mefenamic acid, flufenamic acid, fenoprofin, naproxen, and ibuprofen have been linked to renal papillary necrosis in human beings. Although the exact mechanism of RPN is unknown, there are several theories that have good scientific evidence behind them. Study of RPN in animals as models for the disease in human beings is limited by several factors, including anatomical differences between human beings and most animal species as well as technical difficulties in studying the renal papilla.