As covered in the preceding sections, acute renal failure (ARF) is a syndrome associated with high mortality in humans. Current therapy is limited to supportive measures and preventive strategies, none of which have been definitively shown to alter mortality. Ischemic ARF is often associated with multiple organ failure and sepsis. Despite the complexity of multi-organ illness, the presence of ARF independently carries a marked increase in mortality (1). This review is a brief treatment of our current understanding of the pathophysiology of experimental ischemic ARF and some recent advances in this field. We will first discuss the vasculature. In this context we will consider vasoconstriction as well as endothelial injury. This will lead naturally into the important contribution of inflammation. The response of the epithelial cell and its role in the pathophysiology will then be discussed. In this context, the effects of ischemia on survival of these cells will be supplemented by a discussion of their role as potential contributors to the injury itself. Since ARF is a reversible disease, the manner in which the epithelium is regenerated both anatomically and functionally will be described. We will then discuss the property of the kidney to undergo preconditioning whereby it is protected against a subsequent ischemic insult. Finally we will discuss the status of biomarker research, as the latter is critical to allow for early diagnosis of ARF and evaluation of therapeutic effectiveness as well as for the rational design of human clinical trials.