Based on the conflicting data that we currently have regarding the risk of low HDL-C and therapies to increase HDL-C, how should clinicians and researchers proceed at present? As illustrated in the present report by deGoma et al. (28) in the Veterans Administration study, low levels of HDL-C are certainly potent predictors of CHD risk, even in the setting of quite low and desirable levels of LDL-C. We believe that HDL-C remains a viable target for reduction of CHD, particularly when using proven therapies (e.g., exercise training [(34- 36)], weight reduction [(36- 37)], moderate doses of alcohol [(32)], niacin [(38- 41)], and certain fibrates [10- 12,42]) that not only raise HDL-C but also stimulate RCT, translating into a reduction in CHD risk. At times, however, epidemiologic and preclinical studies (e.g., hormone replacement regimens, antioxidant vitamins, and so on), including that with a new and previously untested HDL-C intervention, torcetrapib (20), have not lived up to their promises and, in fact, have led us astray. However, it should be emphasized that raising HDL-C by all other means has been shown to be safe and effective, and, as yet, the only exception has been CETP inhibition. Therefore, we should not throw out the baby with the bath water. The “bust” with CETP inhibition (at least with torcetrapib) does not mean that we should abandon other HDL-C–elevating therapies. Nevertheless, future new classes of HDL-C therapies should focus on the quality (especially that which stimulates RCT), not just the quantity of HDL-C, and will require absolute proof of benefit and safety from large-scale randomized, controlled trials assessing CHD events, noncardiovascular morbidity and mortality, and all-cause mortality.