Background: Heart failure (HF) is the fastest growing cardiovascular syndrome in the United States and the most common reason for hospitalization of Medicare recipients. HF is prevalent, costly to society and complex to manage. The purpose of this body of work was to strengthen the evidence base for self-care by studying understudied aspects of HF self-care maintenance. Methods/Results: This body of work entails four discrete studies. The first study identified modifiable predictors of patients who are at risk of consuming a diet higher in sodium than recommended by the 2010 Heart Failure Society of America guidelines. The second study identified two unique patterns of sodium intake, "very high" (mean 4.5 g/day) and "generally adherent" (mean 2.4 g/day). Predictors of the very high sodium intake group were being obese, having diabetes mellitus and less than 65 years old. The third study identified unique patterns of inflammation and myocardial stress in a sample of patients with HF from the Heart Failure: A Controlled Trial Investigating Outcomes of Exercise TraiNing (HF-ACTION) clinical trial. Predictors of the worst biomarker pattern were identified and exercise was protective for being in the worst biomarker pattern. In response to these studies, the Motivational Interviewing Tailored Interventions for Heart Failure patients (MITI-HF) randomized controlled trial was designed and conducted to test the efficacy of a tailored motivational interviewing approach to improve self-care, physical HF symptoms and quality of life in patients with HF. Motivational interviewing was a successful approach for improving self-care maintenance, but there were no differences between groups for self-care management, self-care confidence, physical HF symptoms or quality of life. Conclusions: In the context of the rising prevalence of HF within an environment of increasing cost-conscious appropriation of healthcare resources, this body of work provides evidence for targeting self-care interventions to patients who are at highest risk of poor outcomes. It also provides evidence that motivational interviewing is a successful approach for improving self-care maintenance behaviors, specifically eating a lower sodium diet and exercising.