Assuming that blood pressure is lowered equivalently, diuretics are more effective than angiotensin-converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and alpha-adrenergic receptor blockers (alpha-blockers) at preventing heart failure, and they are more effective than ACEIs and alpha-blockers at preventing strokes. Compared with beta-adrenergic receptor blockers (beta-blockers) and ACEIs, CCBs are less effective at reducing myocardial infarcts and heart failure. There is currently no conceptual framework by which to organize data indicating that some antihypertensive medications are better than others at preventing cardiovascular diseases. The thesis of this article is that the fluid reduction or fluid retention attributable to antihypertensive medications, either alone or in combination, provides a basis for ranking these medications. Diuretics have a theoretical advantage compared with other antihypertensive medications because they reduce total body fluid more than other agents. Therefore, they are the preferred drugs for treating hypertension. The other antihypertensive agents that promote fluid reduction, ACEIs and angiotensin receptor blockers (ARBs), are next in preference, ranking a close second to diuretics. Because beta-blockers have a neutral effect on total body fluid, they rank on a third tier of preference, after ACEIs and ARBs. CCBs and alpha-blockers are the least preferred medications for treating hypertension because they promote fluid retention.