Acute liver failure is defined as hepatic insufficiency (icterus and coagulopathy), hepatorenal syndrome and encephalopathy, associated with a high mortality. A number of conditions can cause this sudden severe liver failure, which finally triggers a multi-organ response. Its etiology shows considerable geographic variation, with viral hepatitis being the most common cause worldwide, whilst drugs, especially acetaminophen-induced hepatotoxicity, form the most common precipitant in many developed countries. The essential feature of a wide variety of agents is apoptosis and/or necrosis of liver cells which is associated with liver injury and insufficiency. Based on new experimental data, the identification of target molecules involved in apoptosis may offer new therapeutic options and improvement of prognosis scores in patients with acute liver failure.