Serine hydroxymethyltransferase (SHMT) catalyzes the reversible conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylene tetrahydrofolate (5,10-CH2-THF). The reaction requires pyridoxal-phosphate (PLP) as a coenzyme. 5,10-CH2-THF is a key intermediate for the biosynthesis of purines, thymidine, choline and methionine and connects amino acid and nucleotide metabolisms. SHMT also catalyzes THF-independent aldolytic cleavage, decarboxylation, racemization, and transamination reactions. SHMT levels have been found to increase by 5–10-fold in cancer cells. Therefore it is considered as a potential target for the development of anticancer agents.