Preoperative fasting was introduced in the 19th century to reduce the risk of aspiration pneumonia while patients were under general anesthesia. During the last decades, the value of preoperative fasting has been questioned, and more liberal guidelines have been proposed, such as the use of preoperative carbohydrate-rich drinks. Here we review both old and new evidence supporting the view that fasting slightly longer than overnight is beneficial for an entirely different purpose: protection against certain types of stress, such as ischemia-reperfusion injury. We provide a framework to explain these benefits as well as future applications and alternatives that could be used to induce the protection afforded by nutritional interventions. Liver Transpl 15:1183-1191, 2009. (C) 2009 AASLD.