Xylazine – also known by street names like “tranq” or “tranq dope” – is a veterinary sedative that has rapidly infiltrated the illicit drug supply in recent years. Unlike opioids, xylazine is not intended for human use, yet it’s being combined with fentanyl and other drugs, causing unprecedented challenges for emergency medical services (EMS). This report provides a comprehensive overview of xylazine and similar emerging non-opioid drugs tailored for EMS.