Xylazine (or tranq), a non-opioid veterinary tranquilizer, is not approved for human use; however, it is quickly spreading through the drug supply with disastrous effects and has been linked to an increasing number of overdose deaths nationwide in the evolving overdose crisis. It is often used knowingly or unknowingly in combination with other drugs, particularly fentanyl. We will examine the physiological effects of this central nervous system depressant on the drug user, signs of overdose and response strategies.