This review synthesizes evidence on malaria folate metabolism and antifolate efficacy in the context of folate supplementation. Findings indicate 1) that there is a dose-dependent effect of folate supplementation on antifolate efficacy and that folic acid doses required for protecting pregnant women from neural tube defects will not decrease antifolate activity; and that 2) 5-methyl-tetrahydrofolate could be administered concomitantly with antifolate without affecting antifolate efficacy, even at high doses.