In this review we describe the influence of modified nucleobases in order to understand the changes they introduce in double and triple helix forming oligomers with the aim to study their potential therapeutic use in the antisense/antigene/ribozyme field. The hybridization properties of the studied modified oligomers depend on the structure of the modified nucleoside, the number of modifications, the selected sequence and the location of the modified nucleoside along the sequence. Unfortunately, most available information is based on melting point determination, eventually CD experiments and only in a few cases on X-ray and NMR studies which makes it difficult to put forward general rules for predicting modified nucleic acid structures. On the other hand, several of the described base modifications allow us to select new oligonucleotides with improved properties in the different application fields.