Acute liver failure arises from an imbalance between liver cell death and regeneration. The severity of the insult determines whether liver cells die by apoptosis or necrosis, and this in turn affects the magnitude of the inflammatory reaction. Liver cell death occurs through complex cellular interactions and is mediated by immunological, inflammatory and chemical components. Regeneration of the liver cell mass also depends on cellular interactions, often involving those same mediators implicated in the injury itself. A greater understanding of these processes will lead ultimately to targeted rational therapy in acute liver failure.