The vision for national and regional health information infrastructures (HII) includes provision of a framework that is supportive of access and integration of health information with the goal of improving the health and safety of individuals, public health systems, and nations. Internationally, prominent examples of national and regional HIIs exist that provide a means for achievement of this goal. However, to fully realize benefits, an explicit mechanism is needed for linking national and regional HIIs with existing knowledge, automated processes and evaluation of the ability of HIIs to meet the information needs of primary recipients. Using the United States' Na-tion Health Information Infrastructure (NHII) as an example, the authors describe expansion of the conceptual framework to explicitly acknowledge the role of access to evidence at the overlap between the three dimensions of the NHII to create an "evidence-based" link between interrelated components. The role of national measures in setting e-communication goals and evaluating the evolving infrastructure in meeting informational needs of users is discussed. Additionally, automated knowledge management tools such as practice guidelines are presented as a means by which access to critical information is delivered to users, in a format that is appropriate for their health literacy level and that provides adequate support for informed decision making.