Modified oligonucleotides and their analogs represent an exciting new class of agents with potential therapeutic and diagnostic applications. Among the most extensively investigated analogs are oligonucleoside phosphorothioates, some of which incorporate 'hairpin' structures at the 3' end and 'chimeras' that bear two modified oligonucleotides, all potential therapeutic candidates. To further enhance their potential, bio-reversible analogs of oligonucleotides have been synthesized. Several isosteric analogs of phosphoric diester oligonucleotides with neutral achiral backbones, and other novel molecules, such as peptide nucleic acids and circular oligonucleotides, are also reported to form stable duplexes with complementary RNA/DNA and are currently under investigation. Additionally, oligonucleotides carrying a variety of fluorescent tags have been used as probes with potential for diagnostic applications.