In conclusion, acetaminophen poisoning now accounts for at least 42% of U.S. acute liver failure cases seen at tertiary-care centers and one third of the deaths. Unintentional overdose is the leading form of acetaminophen hepatotoxicity in U.S. ALF subjects, but suicidal ingestions remain important as well. Susceptible patients include those with chronic pain, depression, and substance abuse, including alcohol. Legislative changes in the United Kingdom leading to restrictions in the sales of acetaminophen have reduced the number of patients dying from or needing transplantation because of acetaminophen hepatotoxicity.33, 41–46 Because most cases in the United Kingdom are considered to be suicidal, they differ in that sense from unintentional cases. Nevertheless, efforts to limit OTC package size and to restrict the prescription of narcotic–acetaminophen combinations (or to separate the narcotic from the acetaminophen) may be necessary to reduce the incidence of this increasingly recognized but preventable cause of ALF in the United States. Educational programs for practicing physicians, pharmacists, and consumers, involving a full discussion of the hazards of this ubiquitous pain reliever and the identification of susceptible groups, seems warranted.