Hepatic encephalopathy is a dysfunction of the central nervous system caused by chronic and acute liver disease. The dysfunction presents a wide spectrum of symptoms—from the undetectable in a standard clinical examination to hepatic coma—and could be caused by both chronic and acute liver diseases. For many years research has been conducted to find a marker that would allow for the accurate, quick, and possibly inexpensive detection of hepatic encephalopathy. Due to the pathogenesis of hepatic encephalopathy, researchers’ attention is focused on markers of damage to the central nervous system. One of the markers of astrocyte damage, known from research in neurology and neurosurgery, is the protein S100B. Published research results so far are inconclusive, but they allow us to look with optimism at the role of S100B as a marker of minimal hepatic encephalopathy (MHE).