This clinical guide outlines the essential role of naloxone as a life-saving opioid antagonist used to reverse the effects of an overdose. It identifies high-risk patient populations who should be prioritized for naloxone access, including those on high-dose opioid therapy or individuals with a history of substance use disorders. The resource details critical prescriber actions, such as mandatory patient education and documentation, while providing a clear step-by-step protocol for administration and post-overdose monitoring. By highlighting the temporary nature of the medication, the guide emphasizes the necessity of emergency medical evaluation even after a successful reversal.