Purpose: Many older adults have inadequate health-related literacy, which is associated with poor health outcomes. Thus, it is important to identify determinants of health literacy. We investigated relationships between health literacy and general cognitive and sensory abilities, as well as education, health, and demographic variables, in a community sample of middle-aged and older adults. Design and Methods: Participants were 314 community-dwelling adults (67% female, 48% African American) diagnosed with chronic heart failure recruited for a pharmacist-based intervention study to improve adherence to chronic heart failure medications. We administered demographic, health, education, cognitive (e.g., processing speed, working memory), and sensory measures, and the Short Test of Functional Health Literacy in Adults (STOFHLA), as part of the baseline condition of this study. Results: STOFHLA scores were lower for participants who were older, less educated, male, African American, had more comorbidities, or scored lower on all cognitive ability measures. Hierarchical linear regression analyses showed that education and cognitive ability were independently associated with the STOFHLA measure and explained age differences in health literacy. Implications: The association of cognitive abilities and literacy has important implications for health literacy models and for interventions to reduce the impact of low health literacy on health outcomes. For example, medication instructions should be designed to reduce comprehension demands on general cognitive abilities as well as literacy skills.