The United States opioid epidemic is fueled by illicit opioid abuse and prescription opioid misuse and abuse. Consequently, cases of opioid use disorder (OUD, opioid addiction), opioid overdose, and related deaths have increased since the year 2000. Naloxone is an opioid antagonist that rapidly reverses opioid intoxication to prevent death from overdose. It is one of the major risk mitigation strategies recommended in the 2016 Centers for Disease Control and Prevention Guideline for Prescribing Opioids for Chronic Pain. However, despite the exponential increase in dispensing and distribution of naloxone, opioid overdose and related deaths have continued to increase; suggesting that the increased naloxone supply still lags the need. This discordance is attributed at least in part to the negative attitude toward naloxone, which is based on the belief that naloxone is only meant for “addicts” and “abusers” (OUD patients). This negative attitude or so-called naloxone stigma is therefore considered a major barrier for naloxone distribution and consequently, overdose-death prevention efforts. This article presents evidence that challenges common assertions about OUD stigma being the sole and direct driving force behind naloxone stigma, and the purported magnitude of the barrier that naloxone stigma constitutes for naloxone distribution programs among the stakeholders (patients, pharmacists, and prescribers). The case was then made to operationalize and quantify the construct among the stakeholders to determine the extent to which OUD stigma drives naloxone stigma, and the relative impact of naloxone stigma as a barrier for naloxone distribution efforts.