Adequate levels of folate are crucial for proper brain and body functioning. Folate deficiencies may lead to an increased risk of depression and poorer antidepressant treatment outcomes, as well as an increased risk of cognitive impairment and dementia. In 1996, the U.S. Food and Drug Administration mandated fortification of grain products with folic acid, which has brought about vast reductions in folate deficiency. However, folate deficiencies may be caused by improper absorption and utilization, often due to genetic polymorphisms. Individuals, therefore, can have insufficient levels or lack needed forms of folate, despite adequate intake. Supplementation with the active form of folate, methyltetrahydrofolate, which is more readily absorbed, may be effective in the prevention and treatment of both depression and dementia.