About 50 years ago, research on the biological function of the element selenium was initiated by the report of J. Pinsent that generation of formate dehydrogenase activity by Escherichia coli requires the presence of both selenite and molybdate in the growth medium. In nature, selenium is predominantly associated with sulfur minerals, the Se/S ratios of which vary widely depending on the geological formation. Because of the chemical similarity between the two elements, selenium can intrude into the sulfur pathway at high Se/S ratios and can be statistically incorporated into polypeptides. The central macromolecule for the synthesis and incorporation of selenocysteine is a specialized tRNA, designated tRNA Sec . It is the product of the selC (previously fdhC ) gene. tRNA Sec fulfils a multitude of functions, which are based on its unique structural properties, compared to canonical elongator RNAs. tRNA Sec possesses the discriminator base G73 and the identity elements of serine-specific tRNA isoacceptors. The conversion of seryl-tRNA Sec into selenocysteyl-tRNA Sec is catalyzed by selenocysteine synthase, the product of the selA gene (previously the fdhA locus, which was later shown to harbor two genes, selA and selB ). The crucial element for the regulation is a putative secondary structure at the 5′ end of the untranslated region of the selAB mRNA. The generation and analysis of transcriptional and translational reporter gene fusions of selA and selB yield an expression pattern identical to that obtained by measuring the actual amounts of SelA and SelB proteins.