Selenium derivatization ( via selenomethionine) of proteins for crystal structure determination via MAD phasing has revolutionized protein X-ray crystallography. It is estimated that over two thirds of all new crystal structures of proteins have been determined via Se-Met derivatization. Similarly, selenium functionalities have also been successfully incorporated into nucleic acids to facilitate their structure studies and it has been proved that this Se-derivatization has advantages over halogen strategy, which was usually used as a traditional method in this field. This review reports the development of site-specific selenium derivatization of nucleic acids for phase determination since the year of 2001 ( mainly focus on the 2'-position of the ribose). All the synthesis of 2'-SeMe modified phosphoramidite building blocks ( U, C, T, A, G) and the according oligonucleotides are included. In addition, several structures of selenium contained nucleic acid are also described in this paper.