The development of acute renal failure (ARF) in the perioperative period continues to be a vexing condition associated with high morbidity and mortality rates which have been unchanged for several decades. In this article I briefly review recent research categorizing pathogenesis of ARF and mechanisms of recovery. Once ARF is established, its maintenance phase is dependent on several mechanisms that interact with cellular integrity. The main focus of the article is on assessing clinical and experimental interventions to prevent ARF. Unfortunately, existing pharmacological and other interventions show a rather limited efficacy in preventing ARF.