Hepatic encephalopathy (HE) is a common complication of acute and chronic liver disease associated with exposure of brain tissue to excessive levels of ammonia produced by intestinal bacteria. Clinical manifestations range from subtle neurologic abnormalities to coma. Because development of HE can reduce survival probability, guidelines for evaluating patients for liver transplantation suggest that patients who develop HE should be considered for transplantation. Various patient factors before transplantation, including the presence of HE and reduced nutritional status, may increase the risk of poor outcomes after transplantation. Therefore, effective management of HE before transplantation, while minimizing the potential impact of negative predictive factors, may improve transplantation outcomes. The most common HE treatments are directed toward reducing systemic ammonia levels, thereby reducing brain exposure to this neurotoxin. The administration of nonabsorbable disaccharides is considered as a first-line therapy for HE, and the antibiotics neomycin and metronidazole are frequently administered, despite a lack of clinical data supporting their efficacy. These agents are associated with adverse events that may reduce nutritional status in patients awaiting transplantation and could contribute to poor posttransplantation outcomes. The nonsystemic antibiotic rifaximin has demonstrated efficacy for the treatment of HE and has a favorable safety profile. Given these data, nonsystemic antibiotics may also provide a safe and effective option for treating HE in the pretransplant setting. This article reviews treatments for HE and the potential impact these treatments may have on pretransplantation status of patients awaiting liver transplantation and on posttransplantation outcomes.