Selenium (Se) is an essential trace element for humans, plants and microorganisms. Inorganic selenium is present in nature in four oxidation states: selenate, selenite, elemental Se and selenide in decreasing order of redox status. These forms are converted by all biological systems into more bioavailable organic forms, mainly as the two seleno-amino acids selenocysteine and selenomethionine. Humans, plants and microorganisms are able to fix twhese amino acids into proteins originating Se-containing proteins by a simple replacement of methionine with selenomethionine, or “true” selenoproteins if the insertion of selenocysteine is genetically encoded by a specific UGA codon. Selenocysteine is usually present in the active site of enzymes, being essential for their catalytic activity. This review will focus on the strategies adopted by the different biological systems for selenium incorporation into proteins and on the importance of this element for the physiological functions of living organisms. The most known selenoproteins of humans and microorganisms will be listed highlighting the importance of this element and the problems connected with its deficiency.