Novel 2′-O,4′-C-ethylene nucleosides have been synthesized as building blocks for antisense and antigene oligonucleotides. 2′-O,4′-C-Ethylene-bridged nucleic acids (ENA^TM) comprising 2′-O,4′-C-ethylene nucleosides have considerable affinity to complementary RNA and double-stranded DNA. Incorporation of 2′-O,4′-C-ethylene nucleosides into oligonucleotides dramatically increase their resistance against exonucleases. In this review, the properties of ENA oligonucleotides and some of their applications as antisense and antigene oligonucleotides are described.