Preparing for and responding to public health emergencies involving medical countermeasures (MCMs) raise often complex legal challenges and questions among response stakeholders at the local, state, and federal levels. This includes concerns about emergency legal authorities, liability, emergency use of regulated medical products, and regulations that might enhance or hinder public health response goals. In this article, lawyers from the U.S. Department of Health and Human Services’ (HHS) Office of the General Counsel (OGC), Centers for Disease Control and Prevention (CDC), and Food and Drug Administration (FDA) discuss federal legal tools that are critical to enhancing MCM legal preparedness for public health emergencies, with an emphasis on the legal mechanisms that can be used to facilitate the emergency use of countermeasures. Specifically, the authors describe the Public Readiness and Emergency Preparedness (PREP) Act and Emergency Use Authorization (EUA) authority, outlining the conditions under which these tools can be utilized and providing examples of how they have supported both pre-event (e.g., doxycycline mass dispensing preparedness for anthrax) and intra-event (e.g., 2009 H1N1 influenza pandemic response) activities.