Hypertension control is rare in clinical practice, particularly in high-risk patients. A large factor is therapeutic inertia deriving from poorly prescribed lifestyle changes, excess monotherapy use, and scarce on-treatment modifications. The use of drug combinations significantly improves blood pressure (BP) control; in particular, fixed combinations improve therapy without increasing daily pill intake, thereby favouring patient compliance and therapy continuation. The most widely used fixed combination is based on thiazide diuretics added to either angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). Several large-scale clinical trials have been conducted showing that these combinations are effective in lowering BP. However, thiazide diuretics can reduce the metabolic benefits derived from renin-angiotensin-aldosterone system (RAAS) inhibitors in high metabolic risk patients. In contrast, ACE inhibitors or ARBs combined with dihydropyridine calcium channel antagonists (DHPCAs) exert a marked antihypertensive effect without decreasing metabolic protection by RAAS blockade. In the recent JIKEI heart study, approximately 60% of patients affected by hypertension, heart failure, coronary heart disease or their combination in the valsartan arm were simultaneously treated with DHPCAs. Of note, a 39% reduction in the primary endpoint of combined morbidity and mortality was reported in the valsartan compared with the non-valsartan arm. Furthermore, in a recent multinational study, 83% of 3161 hypertensive patients treated with valsartan and the DHCPA amlodipine reported a concontrolled BP after 8 weeks of treatment. As expected, amlodipine did not negatively influence the metabolic profile of patients, thereby supporting the role of ARB+DHPCA combinations as effective and promising tools in hypertension treatment. In summary, the combination of ARBs with DHPCAs is an effective strategy in hypertension treatment through synergy between their antihypertensive and vascular protective actions, persistent metabolic benefits deriving from RAAS inhibition, and reduced incidence of side effects.