Vitamin B-6 is a water-soluble vitamin first discovered as a factor that cured dermatitis in rats. There are 6 forms of vitamin B-6 found in mammals. The naturally occurring forms of the vitamin include pyridoxine (PN), pyridoxal (PL), pyridoxamine (PM), and their respective monophosphorylated derivatives (PNP, PLP, and PMP). PN, PL, and PM are converted to pyridoxal 5′-phosphate (PLP) through the consecutive actions of 1) a kinase that phosphorylates the 5′hydroxymethyl group and 2) pyridoxamine phosphate oxidase (PNPO), which acts on PNP and PMP. PLP is the biologically active form of the vitamin that functions as an enzyme cofactor and/or regulator for >140 enzyme-catalyzed reactions. PLP-dependent proteins account for ∼4% of total cellular enzymes. PLP is covalently bound to the active sites of aminotransferases, decarboxylases, racemases, and dehydratases, among other enzymes, through a Schiff’s base between the aldehyde of PLP and the e-amino of an active site lysine. PLP-dependent enzymes play essential roles in amino acid metabolism, glycolysis, gluconeogenesis, glycogenolysis, transsulfuration, polyamine biosynthesis, and synthesis of sphingoid bases (required for myelin formation) and the heme precursor δ-aminolevulinic acid. In energy metabolism, PLP-dependent transaminases allow interconversion of amino acids and intermediates in energy-generating pathways. In the brain, PLP is required for the synthesis of the neurotransmitters serotonin, norepinephrine, epinephrine, and γ-aminobutyrate (GABA), and as such is involved in both neuronal excitation and inhibition. Vitamin B-6 is catabolized through the oxidation of pyridoxal to 4-pyridoxic acid, which is excreted in urine.