One of the recent discoveries in protein biosynthesis was the finding that selenocysteine, the 21st amino acid, is cotranslationally inserted into polypeptides under the direction of a UGA codon assisted by a specific structural signal in the mRNA. The key to selenocysteine biosynthesis and insertion is a special tRNA species, tRNA(Sec). The formation of selenocysteine from serine represents an interesting tRNA-mediated amino acid transformation. tRNA(Sec) (or the gene encoding it) has been found over all three domains of life. It displays a number of unique features that designate it a selenocysteine-inserting tRNA and differentiate it from canonical elongator tRNAs. Although there are still some uncertainties concerning the precise secondary and tertiary structures of eukaryal tRNA(Sec), the major identity determinant for selenocysteine biosynthesis and insertion appears to be the 13 bp long extended acceptor arm. In addition the core of the 3D structure of these tRNAs is different from that of class II tRNAs like tRNA(Sec). The biological implications of these structural differences still remain to be fully understood.