As the opioid crisis continues, the illicit opioid supply does not remain stagnant. As the opioid supply has evolved from predominantly heroin to fentanyl, and now fentanyl containing veterinary sedatives and other high potency synthetic drugs, it has resulted in a direct impact on how individuals access the treatment system the care they need to receive. The changing makeup and pharmacology of the opioid supply is necessitating a more timely and proactive treatment approach to reduce hospital admissions, prevent medical and behavioral health complications and improve clinical outcomes. This presentation outlines the changing illicit opioid landscape, familiarizes attendees with the unique treatment challenges that these substances present, reviews the effectiveness of current treatment approaches, and provides tactics that healthcare providers can implement to enhance patient awareness and successful clinical management.