Ascorbic acid is synthesized by a variety of organisms of the animal and plant kingdoms. Among mammals, however, humans, other primates, and guinea pigs cannot exceptionally produce this vitamin, and as a consequence, they are subject to a vitamin C—deficiency disease, scurvy, if the supply of vitamin C from their diet is not sufficient. The genetic defect causing the inability to synthesize ascorbic acid in these animals arose as a result of a mutation that had occurred during their evolution, and this trait is currently carried in all individuals of the scurvy-prone species. In this sense, scurvy is an unusual type of inborn error of metabolism (Nishikimi and Udenfriend, 1977; Stone, 1967). Besides the above-mentioned scurvy-prone animals, there is a mutant rat strain that suffers from scurvy when fed a vitamin C—deficient diet (Mizushima et al., 1984). In this chapter we will focus on the genetic basis of the incapability of humans, guinea pigs, and the scurvy-prone mutant rat to biosynthesize ascorbic acid. In fact, elucidation of the human genetic defect at the gene level has long been a subject of interest for ascorbic acid research. We will also deal with the recent studies related to biosynthesis of ascorbic acid, including the terminal enzymes of the biosynthetic pathways of ascorbic acid.