A modern approach to the choice of antihypertensive therapy is discussed in this article. Since the introduction of hydralazine and reserpine in 1950, a number of compounds have been proposed for the treatment of hypertension. The 1993 report of the Joint National Committee on Hypertension established four choices: diuretics, beta blockers, ACEIs, and calcium entry blockers. Additionally, alpha and alpha-beta blockers were also recommended. Several pharmacological considerations have been discussed concerning medical therapy of hypertension. In modern therapy, the best approach is individualized therapy, in which three major principles are taken into consideration: (1) The use of diuretics, alpha blockers, beta blockers, ACEIs, or calcium entry blockers, (2) The presence of concomitant diseases, and (3) The use of substitution therapy. Several other factors are discussed such as the cost of medication, drug interactions and combinational therapy.