Selenium is an essential trace element with key roles in health. Unlike other essential trace elements, such as zinc, iron, or copper, selenium can be introduced as selenocysteinyl residues into selenoproteins (e.g., glutathione peroxidase, selenoproteins P) during polypeptide chain biosynthesis or in form of selenomethionyl residues into selenium-containing proteins such as, selenoalbumin. Selenium deficiency has been related to heart failure, cancer, neurodegenerative diseases, Keshan disease, COVID-19 among other pathologies. Selenium dietary supplementation leads to the formation of specific selenoproteins, in which Se occupies the active centre, hence influencing the redox-regulated genes and helping the cell to cope with reactive oxygen species into less reactive molecules. Selenium is also important in reproductive health, being essential for gonadal development, gametogenesis and fertilization, probably because of its ability to modulate the antioxidant defence mechanisms and the redox sensitive pathways. In this chapter, we provide the state-of-the art about the role of selenoproteins in human health, nutrition requirements of this element as well as the analytical methodologies for their determination in biological samples.