Acetaminophen, also called paracetamol or N-acetyl-p-aminophenol, is a popular drug used to temporarily reduce pain and fever. It is available in different strengths and forms, and for a wide range of populations, from children to elderly people. The maximum amount of acetaminophen allowed per day is 4,000 mg for adults and children aged 12 years and older. Although acetaminophen is safe when used as directed, long-term use and exceeding the maximum recommended daily dose can cause acetaminophen toxicity and liver damage. Due to the popularity and accessibility of acetaminophen, the risk of acetaminophen overdose, either by accident or on purpose, is relatively common and it is the leading cause of acute liver failure in Canada and around the world. Approximately 4,500 individuals are hospitalized each year in Canada due to acetaminophen overdose, and about 6% of patients hospitalized for acetaminophen overdose develop liver injuries including acute liver failure that may require a liver transplant or lead to death. The diagnosis of liver toxicity is based on serum levels of acetaminophen and other laboratory tests including liver function tests and a coagulation profile. The Rumack-Matthew nomogram, based on large data of patients not treated with antidote, plots acetaminophen concentration against time of ingestion as a predictor of hepatotoxicity and mortality. When the serum concentration of acetaminophen is above the curve at 200 mg/L at 4 hours and 25 mg/L at 16 hours, patients would have 60% incidence of severe hepatotoxicity and 5% rate of mortality. With 300 mg/L serum acetaminophen concentration at 4 hours and 37.5 mg/L at 16 hours, the incidence of severe hepatotoxicity would be up to 90%, and the rate of mortality would be up to 24%. Using this approach, patients with serum acetaminophen concentration greater than 140 mg/L at 4 hours after ingestion are considered having possible risk of hepatotoxicity, and treatment with N-acetyl-cysteine (NAC) is required. NAC has been indicated in Canada as an acetaminophen poisoning antidote. Several analytical methods for determining acetaminophen levels in human serum/plasma have been reported in the literature including high-performance liquid chromatography, UV-visible spectrophotometry, spectrofluorometric, and gas chromatography-mass spectrometry. When a patient is admitted to hospital or emergency department with actual or suspected acetaminophen overdose, blood samples are taken and sent to central laboratory for analysis of acetaminophen levels in the blood, and the diagnosis is delayed while waiting for the laboratory results. Point-of-care tests, also called bed-side tests or near-patient tests, are quick screening tests that could potentially improve the management of these patients. Several point-of-care tests for acetaminophen detection are reported in the literature, however, their clinical utility compared with laboratory-based diagnostic tests is unclear. This report aims to review the clinical utility and cost-effectiveness of point-of-care devices that measure acetaminophen toxicity for patients with suspected overdose. The report also summarizes the recommendations from evidence-based guidelines regarding the administration of IV N-acetylcysteine for patients with acute acetaminophen overdose.