Itch is a complication of liver disease. It is hypothesized that this type of itch is mediated, at least in part, by increased central opioidergic tone; a peripheral component may coexist. The role of serotonin, bile acids, substance P, and lipophosphatidic acid and the activity of the enzyme that generates it, autotoxin, has been proposed in the pathogenesis of itch. Scratching activity was significantly suppressed in association with the placebo tablet in a controlled, double-blind study; this finding supports the exploration of the placebo effect on the itch sensation and the inclusion of behavioral methodology in clinical trials in patients with this complication of liver disease.