The amino acid glutamine is present in all tissues and it serves several purposes depending on the tissue in question. This chapter is devoted to a discussion of its role in relation to the elevated ammonia levels found in the brain in the context of hepatic encephalopathy (HE), a disturbance of the central nervous system due to liver failure [1] characterized by cognitive, psychiatric, and motor deficits. Early symptoms include reversal of sleep pattern, apathy, hypersomnia, irritability, and personal neglect and HE can progressively lead to coma and death [2]. Brain ammonia homeostasis is functionally associated with metabolism in the liver since this organ is responsible for removal of excess ammonia from the bloodstream. Thus, this chapter is intended to focus on glutamine metabolism in these two organs.