The purpose of the present paper is to review our current understanding of the chemistry and biochemistry of folic acid and related folates, and to discuss their impact on public health beyond that already established in relation to neural-tube defects. Our understanding of the fascinating world of folates and C1 metabolism, and their role in health and disease, has come a long way since the discovery of the B-vitamin folic acid by Wills (1931), and its first isolation by Mitchell et al. (1941). However, there is still much to do in perfecting methods for the measurement of folate bioavailability, and status, with a high extent of precision and accuracy. Currently, examination of the relationships between common gene polymorphisms involved in C1 metabolism and folate bioavailability and folate status, morbidity, mortality and longevity is evaluated as a series of individual associations. However, in the future, examination of the concurrent effects of such common gene polymorphisms may be more beneficial.