After a thorough review of the available literature, it appears that hyperhomocysteinemia is an independent risk factor for CHD. Furthermore, folic acid has been shown to reduce homocysteine concentration. Nevertheless, CHD is a multifactorial process, and many risk factors play a role in its pathogenesis. Several unanswered questions remain regarding the role of folic acid supplementation in hyperhomocysteinemia (Table 3). The absolute homocysteine concentration at which cardiovascular risk increases is not certain, and the magnitude of homocysteine-lowering needed to prevent events is unknown. Consequently, the number needed to treat cannot be calculated for folic acid supplements. Based on these data, the populations in whom to evaluate a homocysteine concentration have yet to be described. Because the POEMs are not yet available, it is unknown whether supplemental folic acid to lower homocysteine concentration will reduce CHD morbidity and mortality. It will take several years before any randomized, controlled trials are done, and primary prevention trials will need to be of very long duration to show any change in outcomes. Widespread use of folic acid supplementation has been recommended, however, and the need for clinical outcomes might be precluded. Even in the absence of outcome data, the potential benefits of using folic acid appear to outweigh any risks. A diet high in folic acid should be encouraged in everyone (Table 4). The FDA-mandated folic acid fortification of enriched grain products is most likely insufficient to lower homocysteine concentrations meaningfully, and a daily multivitamin that contains 400 microg of folic acid should be considered for patients who have documented CHD (especially when other risk factors are absent or in patients with premature atherosclerosis) and men and women who have cardiovascular risk factors, in addition to women of childbearing potential. Folic acid supplementation in the form of a multivitamin once daily is safe and inexpensive and might prevent the development and progression of CHD.