Antihypertensive therapy has been associated with 35 to 40% reduction in stroke incidence and 20 to 25% reduction in myocardial infarction. Antihypertensive drugs have various metabolic and endocrine activities. Their effect on electrolytes and hormones which modify the serum levels of electrolytes (such as aldosterone, angiotensine II and brain natriuretic peptide) is reviewed. Antihypertensive drugs may also modify risk factors for cardiovascular disease such as cholesterol, CRP hs, as well as urate acid and insulin resistance. Diuretics and betablockers increase this resistance whereas, it is decreased by certain enzyme conversion inhibitors and certain angiotensine II receptor blockers, partially through adiponectin release. Endocrine side effects of antihypertensive drugs such as weight gain, diabetes, gout, osteoporosis, impotence are discussed. They may decrease adherence to medication. Therefore we recommend if possible a low dose combination of antihypertensive drugs.