Heart failure is a chronic disease requiring careful attention to self-care. Patients must follow instructions for diet and medication use to prevent or delay a decline in functional status, quality of life, and expensive care. However, there is considerable heterogeneity in heart failure patients' knowledge of important care routines, their cognition, and their health literacy, which predict the ability to implement self-care. Our interdisciplinary team of cognitive scientists with health literacy expertise, pharmacists, and physicians spent 18 years designing and testing protocols and materials to assist ambulatory heart failure patients with their care. Our approach is theory- as well as problem-driven, guided by our process-knowledge model of health literacy as it relates to self-care among older adult outpatients with either heart failure or hypertension. We used what we had learned from this model to develop a pharmacy-based protocol and tailored patient instruction materials that were the central component of a randomized clinical trial. Our results showed improved adherence to cardiovascular medications, improved health outcomes and patient satisfaction, and direct cost reductions. These results demonstrate the value of our interdisciplinary efforts for developing strategies to improve instruction and communication with attention to health literacy, which are core components of pharmacy and other ambulatory healthcare services. We believe attention to health literacy with medication use will result in improved health outcomes for older adult patients with heart failure and other complex chronic diseases.