The mechanisms that underlie tolerance to injury in immature animals and tissues have been a subject of interest since 1670. Observations in neonatal units that premature infants are less prone to develop acute renal failure than adults in critical care units have prompted a series of investigations. Although initially attributed to metabolic adaptation such as increased glycolytic capacity and preservation of high energy phosphate, more recent studies have indicated a prominent role for the heat shock response. Observed modulations of injury by heat shock proteins in the immature kidney have significant implications for advancement of our understanding of renal cell injury in both adults and children.