Immunization Information Systems (IIS) have been under development for over twenty years in the US with systems deployed in nearly every state and territory. Yet no national IIS exists, and no serious discussion is underway for a national strategy for IIS data access. This white paper describes the enablers and barriers for creating a national IIS strategy, as well as various potential models for its development, including the attributes, strengths, and challenges for each proposed option. Finally, suggestions are made for informing US policy in this area moving forward.