The number of patients with cirrhosis in the United States continues to rise, and 30–45% of these patients are expected to develop hepatic encephalopathy. A broad spectrum of clinical manifestations is seen with the disorder, including mental or personality changes, asterixis, decreased energy level, impaired cognition, impaired sleep-wake cycle, decreased hand-eye coordination, psychomotor retardation, and incessant talking. Hepatic encephalopathy is a clinical diagnosis, and several scoring systems have been used to determine the severity of hepatic encephalopathy. The West Haven Criteria appear to be the scoring system most frequently used. Minimal hepatic encephalopathy has been reported to affect 60–70% of patients with cirrhosis and is predictive of the development of overt hepatic encephalopathy. An estimated 10–50% of patients who have undergone a transjugular intrahepatic portosystemic shunt for variceal bleeding develop hepatic encephalopathy. A great amount of attention has centered on the role of ammonia in hepatic encephalopathy, but that role is still largely hypothetical. Lactulose has been used for many years to minimize the effects of hepatic encephalopathy; however, noncompliance with lactulose is a common cause of rehospitalization. The pathophysiology of hepatic encephalopathy is extremely complex, and formal treatment guidelines are grossly outdated. The survival rate after 3 years among patients with hepatic encephalopathy is only 25%.