Summary: Current 2023 ESH and 2024 ESC guidelines define hypertension (HT) as resistant to treatment when appropriate lifestyle measures and treatment with optimal or best tolerated doses of three or more drugs (RAS-blocker, CCB and Thiazide/Thiazide-like diuretic) fail to lower office BP to below 140/90 mmHg. Also resistance to treatment should be confirmed by ABPM/HBPM and seconday forms of HT should be excluded. These patients are referred to as having a true-resistant hypertension (TRHT) phenotype with the prevalence of 5% of the overall treated hypertensive population. TRHT is characterized by increased cardiovascular (CV) risk , higher prevalence of target organ damage and CV complications. Therefore ESH 2023 and ESC 2024 guidelines provide practicing physicians and hypertension experts with the update on preferred use RAS blockers, CCBs and thiazide / thiazide-like diuretics and their various combinations for BP-lowering treatment to treat HT and prevent development of TRH. Finally, ESH 2023 and ESC 2024 guidelines contain recommendations for management of hypertension coexisting with various comorbidities, including HF, CKD, CAD AF and other clinical conditions. The current review hightlights the relevance of optimal pharmacological management of HT and overviews clinical trials that changed the landscape of current antihypertensive strategy in the initial, namely 1st and 2nd steps of treatment of HT and also positively affect target organ damage and CV risk in those patients.