Ambulatory treatment of hypertension depends largely on long-term oral medications to lower blood pressure and delay or prevent cardiovascular morbidity and mortality. Failure to achieve the therapeutic goal may reflect biologic, pharmacologic, or behavioral factors. Ignoring behavioral factors may result in unnecessary or even dangerous regimen escalation. More than half of patients with insufficient reductions in blood pressure display suboptimal medication compliance as assessed by pill count or bioassay. Once-daily dosing may be an important part of enhancing compliance, patient convenience, and regimen simplification; however, drug concentrations may be subtherapeutic when dosing delays or omissions occur. Electronic monitoring data in hypertension, glaucoma, seizure disorders, and other diseases indicate that 50% to 60% of patients adhere well to prescribed regiments, that 5% to 10% adhere poorly, and that the 30% to 45% adhere to an intermediate but markedly variable degree. A growing body of literature offers empirical support for focused and personalized interventions.