Patients receiving extended-release (XR) naltrexone who are having surgery present unique challenges to anesthesia providers, the most obvious of which is an altered response to the effects of opioid agonists. Based on the timing of the last XR naltrexone dose, patients may be refractory to the effects of opioid agonists or potentially more sensitive to dangerous side effects due to receptor upregulation and hypersensitivity. Complicating matters, redosing XR naltrexone soon after opioid use may precipitate opioid withdrawal. We present a case of a 22-year-old woman receiving XR naltrexone for a history of heroin abuse undergoing a thyroidectomy and neck dissection. We discuss the intraoperative and postoperative anesthetic and analgesic planning, as well as solutions to some of the challenges these patients pose.