Since the finding that selenium is an essential micronutrient for our life as well as the discovery of selenocysteine (Sec) as the twenty-first proteinogenic amino acid that is expressed by using the information encoded in genes, research fields in chemical biology and biological chemistry have been expanding to a new paradigm where selenium plays important roles. A number of selenoenzymes, which utilize a selenium atom as the active center, have already been characterized, and their biological functions have been identified. However, the chemistry underlying behind their molecular mechanisms is still not fully understood. On the other hand, selenium is a unique element in organic chemistry because it has lower redox potentials than sulfur, rendering organoselenium compounds attractive in applications to redox catalysts and advanced materials. Moreover, selenium atoms in organic compounds have high affinity toward various polar functional groups located in the proximity, forming weak nonbonded interactions between Se and heteroatoms of main-group elements, such as N, O, halogens, etc. Taking advantage of these characteristic features, we recently demonstrated that applications of selenium to the fields of chemical biology and biological chemistry are quite promising for studying various biological problems, such as molecular design of new antioxidants and characterization of oxidative folding pathways of disulfide-containing proteins. In this review, the recent developments in these fields are summarized, along with our own achievements, from a view point of a paradigm shift from sulfur to selenium. This review is divided into four major sections. After brief introduction, physical chemistry aspects of organic selenium compounds, including bond dissociation energies, redox potentials, conformational propensities, and weak nonbonded interactions, are explained in the first section. In the second section, chemical and biological syntheses of selenium compounds, such as Sec and selenomethionine derivatives, selenopeptides, selenoproteins, and other water-soluble selenium compounds, are described. In the third and fourth sections, recent applications of the selenium compounds to the research fields of chemical biology and biological chemistry, respectively, are summarized. The future scopes are given in Conclusions. © 2013 Bentham Science Publishers.