Acute renal failure (ARF) commonly occurs in critically ill patients. Despite improved dialysis techniques and recent advances in intensive care medicine, mortality from this condition remains unacceptably high. Increased understanding of the factors that mediate cellular injury, such as adenosine triphosphate depletion, intracellular calcium accumulation, and generation of reactive oxygenation species, as well as those that mediate recovery, such as locally produced and systemically released growth factors, provide fresh insights that can be used to develop new strategies to limit renal damage after acute insults and speed the repair process. Exogenous administration of growth factors, adenine nucleotides, and thyroxine, each of which can facilitate recovery of experimental ARF, in addition to factors yet to be identified, is a potentially exciting new therapeutic strategy to improve survival of patients with this condition.