Vitamin B6 in its active form pyridoxal phosphate is an essential coenzyme of many diverse enzymes. Biochemistry, enzymology and genetics of de novo vitamin B6 biosynthesis have been primarily investigated in Escherichia coli. Database searches revealed that the key enzymes involved in ring closure of the aromatic pyridoxin ring (PdxA; PdxJ) are present mainly in genomes of bacteria constituting the gamma subdivision of proteobacteria. The distribution of DXS, a transketolase-like enzyme involved in vitamin B6 biosynthesis as well as in thiamine and isoprenoid biosynthesis and the distribution of vitamin B6 modifying enzymes (PdxH: oxidase; PdxK: kinase) was also analyzed. These enzymes are also present in the genomes of animals. Two recent papers (Ehrenshaft et al., 1999, Proc. Natl. Acad. Sci. USA. 96: 9374-9378; Osmani et al., 1999, J. Biol. Chem. 274: 23565-23569) show the involvement of an extremely conserved protein (a member of the UPF0019 or SNZ family) found in all three domains of life (bacteria, archaea, eukarya) in an alternative vitamin B6 biosynthesis pathway. Members of this family were previously identified as a stationary phase inducible protein in yeast, as an ethylene responsible protein in plants and in a marine sponge, as a singlet oxygen resistance protein in Cercospora nicotianae and as a cumene hydroperoxide and H2O2 inducible protein in Bacillus subtilis. In yeast, the SNZ protein interacts with another protein called SNO which also represents a member of a highly conserved protein family (called UPF0030 or SNO family). Phylogenetic trees for the DXS, PdxA, PdxJ, PdxH, PdxK, SNZ and SNO protein families are presented and possible implications of the two different vitamin B6 biosynthesis pathways in cellular metabolism are discussed. A radically different view of bacterial evolution (Gupta, 2000, Crit. Rev. Microbiol. 26: 111-131) which proposes a linear rather than a treelike evolutionary relationship between procaryotic species indicates that the gamma subdivision of proteobacteria represents the most recently evolved bacterial lineage. This proposal might help to explain why the PdxA/PdxJ pathway is largely restricted to this subdivision.