In this paper, our recent studies on the synthesis of unmodified and modified oligonucleotides are comprehensively reviewed. We have developed a new synthetic strategy using TrS, a new 5'-protecting group, that enabled us to reduce one of the steps previously required for DNA synthesis. The "activated phosphite method" without base protection could provide a new tool for the synthesis of DNA oligomers involving base-labile functional groups such as N-acylated nucleobases capable of Watson-Crick base pairing. This new method was successfully applied to the synthesis of oligodeoxynucleotides incorporating cytosine N-oxide or adenine N-oxide that could not be synthesized by the current methods. Furthermore, several approaches we recently developed for the synthesis of several kinds of 2'-O-modified RNA oligomers will be reported.