This chapter examines the importance of health literacy to the design and use of mobile digital health information technology (mHealth) applications. Over the past two decades mHealth has evolved to become a major health communication channel for delivering health care, promoting health, and tracking health behaviors. Yet, there are serious communication challenges that must be addressed concerning the best way to design and utilize mHealth application to achieve key health promotion goals, including assuring the appropriateness and effectiveness of mHealth messaging for audiences with different communication competencies, styles, and health literacy levels, to ensure that mHealth applications are truly effective tools for health promotion. Health literacy is one of the major communication issues relevant to the effective use of mHealth. To be effective, mHealth applications need to match the messages conveyed via these mobile media to the specific health communication needs, orientations, and competencies of intended audience members. Unfortunately, current evidence suggests that many mHealth applications are difficult for audiences to utilize because they provide health information that is not easy for many consumers to understand and apply. Health literacy refers to the ability of participants within the health care system to accurately interpret and utilize relevant health information and resources to achieve their health goals. Evidence suggests that many consumers possess limited levels of health literacy to adequately understand health information, especially when they are feeling ill, since health literacy is both a trait (limited education, language facility, etc.), and a state condition (based on how their current physical and mental states influence their abilities to communicate effectively). Therefore, it is incumbent upon mHealth developers to design and utilize message systems. Strategies for designing and implementing mHealth applications to meet the health literacy levels of different audiences are described in this chapter.