Although the field of health literacy is experiencing tremendous growth in terms of producing peer-reviewed journal articles and attracting practitioners, the foundation of that growth is potentially unstable. Despite a steady increase in their number, existing measures and screeners of health literacy are not based on an accepted conceptual framework and fail to align with the growing body of theoretical and applied work. Existing measures are mainly focused on assessing what individuals can read and understand in clinical contexts. This leaves important factors untested, such as how individuals use information, and how health professionals and systems communicate with patients. This article outlines key elements of a proposed research agenda focusing on development of a new, comprehensive approach to measuring health literacy.