The aim of the present work was to perform a critical analysis of the literature related to the role of the extrahepatic matrix Gla-protein (MGP) as an inhibitor of vascular calcification. Online databases PubMed, Google Scholar, Scopus, Science Direct, and Medline were thoroughly searched using key words such as Gla protein, Gla rich protein (GRP), matrix GLA protein (MGP), cardiovascular calcification, vitamin K, calcification inhibitor, aortic valve calcification. More than 1400 articles in the last 10 years were found. The structure and the biologic functions of matrix-Gla-protein (MGP) were discussed. MGP is thought to be an inhibitor of vascular calcification, and evidence for this stems from its Ca2+-binding gamma-carboxyglutamic acid motif, inhibition of cartilage calcification, binding and antagonizing BMP-2. The introduction of Gla-residues is by vitamin K-dependent carboxylase. Vitamin K hydroquinone (KH2) is used as the active cofactor in the carboxylation reaction. Upon oxidation of KH2, the released energy is used to introduce an extra carboxyl group at the c-position of a glutamate residue. Discovery of the relationship between the different isoforms of vitamin K and extrahepatic Gla-proteins can be a prerequisite for making an adequate solution for supplementing with vitamin K preparations. Since the methods of bioavailability testing of vitamin K are not applicable in routine practice, various functional forms of extrahepatic vitamin K-dependent Gla-protein MGP can serve as biomarkers for assessing the need for supplementation with vitamin K.