A recently observed decrease in the prevalence of cleft lip with or without cleft palate in the United States was associated with the folic acid fortification of enriched cereal grains, which became mandatory in 1998. Several case-control and one prospective study found an inverse association between intake of folic acid and/or multivitamins and the risk of cleft lip with or without cleft palate. A randomized trial to prove causality would be unethical, due to the established relationship between neural tube defects and periconceptional folic acid use. Until the results of carefully carried out cohort studies will be available, all women of childbearing age not under contraceptives should consume a diet rich in folate and take an additional daily dose of at least 0.4 (better 0.8) mg folic acid, preferably with a multivitamin, and until the end of the first twelve weeks after conception. With these recommendations for the prevention of neural tube defects, the risk of cleft lip with or without cleft palate may also be reduced.