The importance of measurements of the blood ammonia concentration in the evaluation of patients with known or suspected hepatic encephalopathy (HE) is still disputed in spite of a general acknowledgment that ammonia is important in the pathogenesis of the disorder. Several recent studies have suggested that it is not necessary to utilize arterial blood when measuring ammonia in the blood. Venous blood or a computation of the partial pressure of ammonia gas in blood samples may suffice. The value of blood ammonia measurements is limited by the fact that this is not the variable that is the most important. Ideally, one would like to know how much ammonia enters the brain, not how much is in the blood. The blood-brain barrier (BBB) is the critical and poorly understood element in this relationship. Although both ammonia in the gas and ionic forms cross the BBB, the ease with which this movement occurs is significantly higher in patients with HE. In the absence of simple methods to measure the brain ammonia metabolic rate and to assess the BBB to ammonia in conjunction with measuring the blood ammonia concentration, the variables that would be the most desirable to measure, the use of arterial and/or venous blood measurements needs to be coupled with a complete understanding of the physiology of cerebral ammonia metabolism.