Xylazine is a sedative, analgesic and muscle relaxant widely applied in the veterinary field. However, owing to its depressant effect, xylazine has become a substance of abuse by humans. Misuse of xylazine not only triggers unwanted consequences (death), but also linked with various crimes. Google Scholar, PubMed and SciFinder were used to retrieve articles and case reports in relation to the misuses of xylazine and established analytical methods for forensic investigation until November 2021. Literatures reported the accidental and intended poisoning of xylazine, recreational use of xylazine and as an adulterant in recreational drugs. In addition to being a facilitator of crime and sexual assault, it is administered illegally to food producing animals as a sedative and to sports animals as a doping agent. Problems associated with the abuse of xylazine were highlighted in this review, covering the unknown prevalence of xylazine abuse and the need to revise the regulatory status of xylazine. In addition, limited screening and confirmatory methods that can be readily utilised to detect xylazine either alone or simultaneously with other substances of abuse, particularly useful for forensic toxicology and narcotic section were available in the literature. As a conventionally used veterinary drug, xylazine is undoubtedly a potentially hazardous drug, and the investigations on its potential abuse would enhance routine forensic examination to keep pace with the status of illicit drugs.