Major trials evaluating antihypertensive therapy are reviewed, and the current issues surrounding the choice of therapy in mild and isolated systolic hypertension are discussed. Several major trials have shown that patients with mild hypertension benefit from therapy. These results have prompted widespread use of antihypertensive agents; however, there are still no clear guidelines on when drug therapy should be initiated. Only the Hypertension Detection and Follow-up Program has shown significant decreases in coronary heart disease (CHD) related deaths. Thiazide diuretics are recommended as agents of first choice in the stepped-care approach to the management of uncomplicated mild to moderate hypertension. The Multiple Risk Factor Intervention Trial evaluated the effects of modifying several cardiovascular risk factors in more than 12,000 high-risk men. It failed to document significant differences in CHD-related mortality in patients who received special care as compared with those who received usual care. Concerns have been raised about the contribution of antihypertensive therapy, particularly diuretics, to the lack of differences in therapeutic outcomes. There is renewed interest in lipid alterations secondary to antihypertensive agents and the effect of diuretic-induced hypokalemia. Antihypertensive therapy should be instituted with an individualized assessment of the potential benefits of therapy relative to the short- and long-term risks of treatment.