In this presentation, Dennis Goodstein, PharmD, BCPS, and Emily Casey, PharmD, BCPMP, provide an overview of medetomidine, an increasingly prevalent adulterant in the illicit drug supply that is changing overdose and withdrawal presentations across Philadelphia and beyond. Participants will learn how to recognize the clinical signs of medetomidine intoxication and withdrawal, understand how medetomidine differs from xylazine, and explore current trends in the evolving drug supply. The session reviews evidence-informed approaches to overdose response, emergency and outpatient management, and community-based care, with a focus on the use of alpha-2 agonists, antiemetics, and medications for opioid use disorder (MOUD). Practical guidance is provided to help healthcare professionals identify medetomidine-related complications, respond effectively to overdose events, and support individuals experiencing withdrawal in a variety of clinical and community settings.