In this review, Dr. Silva-Torres and colleagues summarize current evidence on xylazine misuse, a veterinary tranquilizer that has rapidly emerged as a dangerous adulterant in illicit drug supplies. They discuss how xylazine is increasingly detected in combination with opioids such as fentanyl, substantially raising the risk of overdose and death, and how its pharmacological effects, including profound sedation and respiratory depression, complicate both clinical management and forensic detection. The authors also highlight ongoing public health and policy challenges in monitoring and responding to this growing threat, given xylazine’s expanding role in the opioid epidemic.