The major risk factors for coronary heart disease remain high blood pressure, cigarette smoking, and abnormal serum lipid levels, including total cholesterol but more specifically elevated low-density lipoprotein cholesterol and reduced high-density lipoprotein cholesterol levels. Observations made from large-scale trials almost a decade ago suggested that commonly used antihypertensive agents, such as thiazide diuretics and beta-blockers, may adversely influence serum lipid levels. Over time, we realized that these lipid alterations persist long term and are of sufficient magnitude to potentially account for important differences in coronary heart disease risk reduction among various antihypertensive drug regimens. Considering recent National Cholesterol Education Program and Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure recommendations concerning lipid and blood pressure treatment, it is prudent and timely to rethink our approach to antihypertensive therapy in patients with abnormal serum lipid levels. Therefore, when lipids are a concern, appropriate dietary treatments should be advised and antihypertensive therapy that has a beneficial or neutral impact on serum lipid levels should be considered.