Hepatic encephalopathy is a neuropsychiatric disorder; a major complication of liver disease. Impairment in liver function leads to a reduced capacity to clear ammonia (via urea cycle) and subsequently hyperammonemia arises. The consequent neurotoxic levels of ammonia are considered to play a major role in the pathogenesis of hepatic encephalopathy. However, a correlation between ammonia and severity of neurological impairment is poor. Oxidative stress is another factor believed to play a role in the pathogenesis of this syndrome as it has demonstrated to exacerbate the neuropsychological effects of hyperammonemia. In the setting of liver disease, oxidative stress represents a systemic phenomenon induced by several mechanisms: decreased antioxidant synthesis, increased systemic release of oxidant enzymes, generation of reactive oxygen species and impaired neutrophil function. Furthermore, it has been demonstrated that high ammonia concentrations can induce oxidative stress. However, significantly lower degrees of hyperammonemia (<500 µM) are observed in patients with end-stage liver disease (cirrhosis), concentrations which do not induce cerebral nor systemic oxidative stress. Therefore defining ammonia and oxidative stress as independent factors. Data from both animal and human studies strongly suggest there is a synergistic effect between systemic oxidative stress and ammonia in the pathogenesis of hepatic encephalopathy and that induction of cerebral oxidative stress may be associated with severe neurological symptoms.