Hepatic encephalopathy is a neuropsychiatric syndrome associated with acute liver failure, chronic parenchymal liver disease, or portosystemic anastomosis. Many approaches have been used to develop suitable models of hepatic encephalopathy, each with specific advantages and disadvantages. The most commonly used models have been the surgical hepatectomy and liver devascularization procedures, and hepatotoxins such as galactosamine and acetaminophen. Drug-toxicity models may be clinically more relevant. The specific requirements of experiments to study a particular aspect of encephalopathy also influence the choice of animal model. Animal models will play a central role in future research into hepatic encephalopathy to better understand its pathophysiology and to develop newer therapeutic modalities for this condition.