Although N-acetyl-cysteine (NAC) has long been used for the treatment of acetaminophen poisoning/overdose, the optimal NAC dosing regimen for varying patterns or severity of the poisoning/overdose is still unknown.Relevant literature was searched for in the MEDLINE (from 1964 until August 31st, 2022), SCOPUS (from 2004 until August 31st, 2022) and GOOGLE SCHOLAR (from 2004 until August 31st, 2022) databases, without restriction in terms of publication date. The inclusion criteria were: original clinical studies reporting results, and studies investigating efficacy and safety of NAC dosing regimens in case(s) of overdose or poisoning with acetaminophen.For a more effective treatment of acetaminophen poisoning in the future, it will be crucial to advance the technology of measuring acetaminophen, its metabolites and NAC in the serum, preferably with the point-of-care technique, so that in real time it can be continuously assessed whether it is necessary to administer NAC, and further to increase the dose of NAC and extend the duration of its administration, or not.