It is proven that folic acid supplied in the periconceptional period can lower the recurrence and occurrence rate of neural tube defects (NTDs). Our research team on prevention of birth defects could demonstrate that folic acid preventable NTDs are partly based on hyperhomocystinemia and a genetic predisposition (mutation of the methylenetetrahydrofolate-reductase gene (MTHF-R)). Reduced activity of the folate methylation cycle seems to be an attractive working hypothesis in the aetiology of NTDs. This genetic metabolic defect can be overcome by treatment with folic acid and/or vitamin B12.