This chapter describes drug treatment for hypertension. After more than 80 years of hypertension research and much talk about the newer drugs, sadly only four classes of antihypertensive agents are available to treat more than 1.2 billion individuals with hypertension following as diuretics, beta-blockers, calcium antagonists, and angiotensin-converting enzyme (ACE) inhibitors. This chapter covers the common detrimental effects of hypertension, safety first for patients, hallmark randomized clinical trials, angiotensin-converting enzyme inhibitors cause angioedema, diabetics, diuretics, diuretics for treatment of hypertension in the elderly, beta-blockers, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, and hypertensive crisis. Angiotensin-converting enzyme inhibitors cause angioedema requiring emergency room (ER) visits and deaths have been reported. Causing death, albeit rare, is not acceptable. Angiotensin receptor blockers can replace ACE inhibitors for the treatment of hypertension.