Summary: In the 2023 ESH guidelines, five major drug classes were recommended as first-line agents for the treatment of hypertension, i.e. ACEis, ARBs, CCBs, thiazide/thiazide-like diuretics and BBs. Angiotensin receptor blockers (ARBs) have a similar antihypertensive efficacy and protective effect as ACEis with a somewhat different mechanism for RAS inhibition. A difference between ACEis and ARBs is their tolerability profile, with ARBs having a rate of side effects similar to placebo. ARBs are associated with the lowest treatment-discontinuation rate when compared with all other antihypertensive therapies. With several compounds’ availability, the class of ARBs represents a relatively homogenous class of drugs. Based on the results of outcome RCTs, recent meta-analyses and evidence of BP-lowering effectiveness, all five major drug classes can in principle be combined with one another, except for ACEis and ARBs. However, ESH 2023 Guidelines recommend that treatment of hypertension should be preferentially based on combinations of ACEi or ARB with CCB or a thiazide/thiazide-like diuretic. These combinations are now widely available in a single pill and in a range of doses, facilitating flexible prescribing and up-titration from lower to higher doses. This review also focuses on the role of valsartan in the treatment of hypertension – many studies have demonstrated the efficacy of valsartan in lowering blood pressure (BP) in a variety of patient populations including elderly, obese patients, patients with diabetes mellitus, patients with chronic kidney disease (CKD), patients at high risk of cardiovascular (CV) disease and in improving outcomes in CV disease and CKD. In hypertension, valsartan exhibits dose-dependent efficacy in reducing both systolic and diastolic BP and BP control can be enhanced with a more consistent 24-hour BP-lowering profile by using single pill fixed-dose combination therapy with valsartan plus hydrochlorothiazide (HCTZ). Valsartan has a more favourable tolerability profile in comparisn with ACEi, with a significantly lower incidence of cough.