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Background: Paracetamol or acetaminophen (APAP), or acetaminophen, is a widely used medication for pain relief and fever reduction due to its analgesic and antipyretic properties. However, excessive APAP consumption can lead to severe hepatotoxicity and nephrotoxicity, posing overdose risks. Consequently, the development of analytical methods for an accurate and rapid detection of APAP in biological matrices is of great interest in the health-related fields. Electrochemical methods have emerged as efficient, cost-effective, and sensitive tools for APAP detection in biological samples. In the light of the reported insights, this review examines critically diverse electrochemical methods for PAR detection in different biological matrices, including serum, urine, oral fluid, and sweat., Results: The claimed benefits of chemically-modified electrodes towards the selective determination of paracetamol in such complex sample matrices are discussed. On the other hand, the possible use of unmodified carbon-based electrodes combined with flow methods is highlighted as an alternative that can find relevance in the analysis of biological fluids suspected of PAR overdose occurring in the forensic scenario. Furthermore, the details regarding the distinct techniques and working electrodes for APAP determination are presented, compared and discussed in separate sections for each biological sample (serum, urine, and oral fluid). Another aspect herein debated is the selective determination of APAP in the presence of electroactive drugs naturally found in biological samples, as uric acid, and ascorbic acid, are evaluated. In addition, we have discussed and emphasized the significance of matrix selection to ensure precise results, especially in potential overdose scenarios., Significance: This review article provides a critical discussion on the development of electroanalytical methods for biological fluids, with relevance to the fields of clinical analysis and forensics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)