An estimated 71 million individuals in the United States are currently diagnosed with cardiovascular disease (CVD). If untreated, CVD conditions such as systemic hypertension, coronary artery disease, and heart failure will have potentially serious and often fatal outcomes. Numerous clinical trials have established a variety of evidence-based medications that are efficacious in the treatment of CVD. These drugs will be ineffective, however, if patients have trouble adhering to their prescribed regimens. In patients with hypertension or heart failure, or in those who have suffered a myocardial infarction, poor adherence to therapies has been linked to a variety of problems, including poor blood pressure control, rehospitalization, and increased healthcare resource utilization. Both the asymptomatic nature of some forms of CVD and the high pill burden associated with certain therapies have been linked to poor adherence. Reducing pill burden through the use of once-daily formulations has proven valuable in improving adherence to evidence-based therapies. This review will discuss the impact of adherence to prescribed therapies for CVD, outline common barriers to adherence, and demonstrate the value of once-daily dosing regimens for improved patient adherence.