Hepatic ischemia/reperfusion (I/R) results in a chain of events that culminate in liver dysfunction and injury. I/R injury is characterized by early oxidant stress followed by an intense acute inflammatory response that involves the transcription factor nuclear factor (NF)-kappaB. In addition to being a primary regulator of pro-inflammatory gene expression, NF-kappaB may play other roles in the hepatic response to I/R, such as mediating the expression of anti-apoptotic genes, preventing the accumulation of damaging reactive oxygen species, facilitating liver regeneration, and mediating the protective effects of ischemic preconditioning. In the present study, we review the diverse functions of NF-kappaB during hepatic I/R injury.