Abstract Protein N-glycosylation is an ancient metabolic pathway that still exists in all three domains of life (Archaea, Bacteria and Eukarya). The covalent addition of one or more complex oligosaccharides (glycans) to protein backbones greatly diversifies their structures and makes the glycoproteome several orders of magnitude more complex than the proteome itself. Contrary to polypeptides, which are defined by a sequence of nucleotides in the corresponding genes, the glycan part of glycoproteins are encoded in a complex dynamic network of hundreds of proteins, whereby activity is defined by both genetic sequence and the regulation of gene expression. Owing to the complex nature of their biosynthesis, glycans are particularly versatile and apparently a large part of human variation derives from differences in protein glycosylation. Composition of the individual glycome appears to be rather stable, and thus differences in the pattern of glycan synthesis between individuals could originate either from genetic polymorphisms or from stable epigenetic regulation of gene expression in different individuals. Studies of epigenetic modification of genes involved in protein glycosylation are still scarce, but their results indicate that this process might be very important for the regulation of protein glycosylation.