Carbohydrates are one of the most structurally complex and functionally diverse groups of organic molecules in living organisms. They can be identified as free molecules or can be found in conjugated structures forming compounds with proteins and lipids. Around half of all proteins expressed in human cells are glycosylated in the endoplasmic reticulum and Golgi apparatus, in order to achieve full functionality. There are N and O types of protein glycosylation depending on the place of insertion of the oligosaccharide. The biosynthesis of glycan is not templatedependent, but it is indirectly controlled by the genes expression of glycosyltransferase and glycosidase, which catalyze the biosynthesis of the glycans. N-glycosylation process is characterized by the formation of the precursor of 14 carbohydrate residues on the dolicol molecule that consist of 3 molecules of glucose, 9- mannose, and 2- N-acetyl-glucosamine, by transferring the precursor from the dolicol molecule to the protein, by processing and maturation of glycoprotein in AG, by elongation and development of antennas and by capping. Defects in glycosylation process form a group of inherited errors of metabolism, genetically determined by autosome-recessive transmission, known as Congenital Defects of Glycosylation (CDG). These rare conditions, characterized by multisystem damage, cause a severe neuropsychomotor retardation. Although the first clinical description of CDG was in 1980, currently about 150 types of CDG are described. The CDG Ia type, caused by phosphomanutase-2 deficiency that catalyze the transformation of mannose-6-phosphate in mannose-1-phosphate, is one of the most common type with incidence around 62% in CDG patients. Along with this, other forms of CDG have been described: CDG Ib is caused by mutations in the MPI gene that perturb the transformation of fructose into mannose; CDG IIa resulted from deficiency of MGAT2 gene encoding N-acetylglucosaminyl transferase II that add one molecule of N-acetylglucosamine to the glycan and another types that are not so frequent. In conclusion, glycosylation is a common and complex process which alteration lead to very vast spectrum of clinical manifestation with negative multisystem consequences on normal function of metabolism.