Hypertension is a major modifiable risk for the development of cardiovascular, cerebrovascular and renal diseases. Thus, effective treatment of high blood pressure is an important strategy for reducing disease burden; however, in spite of the availability of numerous effective therapies only 30–40 % of patients with hypertension achieve the recommended blood pressure goals of <140/90 mmHg. Lack of adherence to therapy and reluctance to intensify therapy are cited frequently to explain the discrepancy between potential and attained outcomes. Adherence is closely related to the tolerability, effectiveness and complexity of therapy. Therapeutic inertia may be influenced by concerns over tolerability, as well as the lack of clear preferences for therapies when managing patients with risk factors and comorbidities. Effective and well-tolerated single pill combination therapies are now available that improve adherence and simplify treatment. The combination of a renin-angiotensin system blocker with a calcium channel blocker and a diuretic improves adherence to therapy. We have devised a practical tool for orienting the application of well-tolerated single pill 2/3 drug fixed dose combination therapies in clinical situations commonly encountered when treating hypertensive patients. This approach employs the angiotensin receptor blocker olmesartan alone or in combinations with amlodipine and/or hydrochlorothiazide. This platform is based on clinical evidence, guidelines, best practice, and clinical experience where none of these is available. We believe it will increase the percentage of hypertensive patients who achieve blood pressure control when applied as part of an integrative approach that includes regular follow-up and instruction on lifestyle changes.