Hepatic ischemia-reperfusion injury (IRI) occurs upon restoration of hepatic blood flow after a period of ischemia. Decreased endogenous nitric oxide (NO) production resulting in capillary luminal narrowing is central in the pathogenesis of IRI. Exogenous NO has emerged as a potential therapy for IRI based on its role in decreasing oxidative stress, cytokine release, leukocyte endothelial-adhesion and hepatic apoptosis. This review will highlight the influence of endogenous NO on hepatic IRI, role of inhaled NO in ameliorating IRI, modes of delivery, donor drugs and potential side effects of exogenous NO. © 2010 Baishideng.