More than 50 years of high-quality data demonstrate that naloxone is an efficacious and cost-effective overdose reversal agent. Intranasal naloxone is now available in the United States as an over-the-counter and generic medication for the first time since the start of the overdose crisis more than 20 years ago. As the overdose crisis continues to contribute to substantial loss of life, there is an historic opportunity for jurisdictions to expand equitable and sustained access to intranasal naloxone. Further, through simultaneously enacting and expanding effective Naloxone Access and Good Samaritan laws, and equitably implementing these laws, there is the potential to maximize the population-level effectiveness of naloxone to sustainably reduce overdose mortality.