Ischemic injury to the kidney is associated with high morbidity and mortality. Improving the ability of the kidney to tolerate ischemic injury would have important implications. A significant amount of data now exists to suggest that there may be intrinsic mechanisms brought to bear by the kidney when exposed to a toxic or ischemic insult, which protect it against a subsequent exposure to ischemia. While it is frequently stated that this phenomenon, termed ischemic preconditioning, was first described in the heart, in fact there is almost a century of literature on the kidney that supports the concept that prior injury protects against a second insult. The protective effect of preconditioning is greater than most reported protective effects with pharmacological interventions in animals. There is compelling evidence in other organs that preconditioning occurs in humans. It therefore behooves us to understand the endogenous processes that the kidney has developed to protect itself against an ischemic insult. Armed with this understanding we can then attempt to mimic these processes and thereby prevent and treat ischemic acute renal failure.