Achieving optimal outcomes in the treatment of hypertension—a prevalent and largely asymptomatic disease—necessitates that patients take their medications not only properly (medication adherence) but also continue to do so throughout long-term treatment (persistence). However, poor medication-taking behavior is a major problem among patients with hypertension, and has been identified as one of the main causes of failure to achieve adequate control of blood pressure (BP). In turn, patients with hypertension who have uncontrolled BP as a result of their poor medication-taking behavior remain at risk for serious morbidity and mortality (eg, stroke, myocardial infarction, and kidney failure), thereby accounting for a significant cost burden through avoidable hospital admissions, premature deaths, work absenteeism, and reduced productivity. Improving medication-taking behavior during antihypertensive therapy therefore represents an important potential source of health and economic improvement. Whereas many factors may contribute to poor medication-taking behavior, the complexity of dosage regimens and the side effect profiles of drugs probably have the greatest therapy-related influence. Central to any strategy aimed at improving outcomes for patients with hypertension, therefore, are efficacious antihypertensive agents that facilitate good medication-taking behavior through simplified dosing and placebo-like tolerability, along with the development of programs to detect poor medication adherence and to support long-term medication persistence in daily practice.