The pathophysiology of HE has not yet been clarified. At present the main mechanisms under discussion are the combined effects of different toxins, such as ammonia, mercaptans, phenols and short- and medium-chain fatty acids, as well as a change particularly in GABAergic and glutamatergic neurotransmission. In this chapter the current views on the importance of these individual factors in the pathophysiology of HE are discussed; possible connections between changes in neurotransmission and the effect of different neurotoxins are presented. In addition, possible therapies resulting from recent knowledge of the pathophysiology of this disease are discussed, such as the use of Bz receptor antagonists.