Haemorrhage during resection of the liver remains a significant threat to clinical outcome. Portal triad occlusion, with complete clamping of the hepatic inflow at the hepatoduodenal ligament, is a well-documented, safe, and useful means of alleviating this problem. Although this technique is effective in limiting blood loss, there is still controversy concerning the potential drawbacks of ischemia and subsequent reperfusion injury of the liver. This article highlights recent advances in our understanding of the clinical factors influencing ischemia-reperfusion injury of the liver, particularly in human patients. These factors include the cell components involved, the mechanisms that enable the human liver to tolerate long-term inflow occlusion, factors affecting clinical outcomes, and surgical and pharmacological techniques used to alleviate ischemia-reperfusion injury, including hypothermic hepatectomy.