The recent shift of products from prescription-only to over-the-counter in the U.S. indicates a potential surge in similar changes. Oral contraceptive Opill and opioid antagonist Narcan have transitioned, influencing their accessibility. However, with limited product accessibility without a prescription behind-the-counter, the increase in such changes will be restrained. The Rx-to-OTC switch process is based on various safety and effectiveness studies, while recent history shows a rise in switch activity. The absence of a formal third class of drugs in the U.S. may hinder novel switches, unlike in overseas markets. The introduction of the Nonprescription Safe Use Regulatory Expansion (NSURE) initiative aimed to facilitate switches in new therapeutic classes, but its impact has been limited. The potential for Rx-to-OTC switches in various therapeutic categories remains, but challenges persist.