Non-adherence with medical regimens in heart failure is a significant challenge and serves as a major reason that favorable outcomes associated with various therapies evaluated in clinical trials have not translated to the so-called real-world setting. Non-adherence has complex influences and is clearly associated with poorer outcomes. The approaches that are used or have been proposed to improve drug-taking behavior, such as in-hospital initiation of therapy, simplification of dosing regimens through adoption of combination and long-acting formulations, and improvements in provider-patient communication, are reviewed.