Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?