Selenium derivatization is a powerful tool for structure and function studies of nucleic acids. The distinct steric and electronic properties of selenium have facilitated the X-ray structural analysis of DNA and RNA as well as their interactions with proteins. Notably, this technique has been applied for the investigation of ribozymes, riboswitches, homo-DNA, and for HIV-1 drug discovery. Besides their application in X-ray crystallography, selenium-modified nucleic acids are potential therapeutics for the treatment of cancer, as well as viral or bacterial infections. In addition, they have attracted interest as diagnostic agents. Several types of selenium derivatization of nucleic acids have been described which include replacement of an oxygen atom by selenium either in the nucleobase, the sugar moiety or in the phosphate groups of a nucleoside or nucleotide (please see for reviews).