Acute liver failure is a rare and devastating clinical condition. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multiorgan failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognised. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research. At present, emergency liver transplantation is the only life-saving therapy in advanced cases, yet the feasibility of transplantation is affected by the presence of systemic inflammation, infection and resultant multiorgan failure. The importance of immune dysregulation and acquisition of infection in the pathogenesis of acute liver failure and its associated complications is now recognized. In this review we discuss current thinking regarding the role of infection and inflammation in the pathogenesis of and outcome in human acute liver failure, the implications for the management of such patients and suggest directions for future research.