Public health concerns underlie a considerable portion of the global burden of disease, increasing the utility and need for promoting and assessing the knowledge about public health issues. Health literacy is generally agreed upon as a means to find, understand, analyze and use information to make better decisions about health and to ultimately reduce inequities in health. A public health literacy knowledge scale was tested in China, Mexico, Ghana and India. A somewhat unexpected finding, which was that experts ‘scored’ less on the scale than the general public, led to consideration of differences between clinical and public health approaches to health literacy and their implications. These differences in perspective, for instance consideration of single case effects versus impacts at the societal level, pose significant challenges to developing and assessing health literacy. We suggest that a comprehensive approach to health literacy will include both clinical and public health approaches.