Glycoconjugate vaccines have been effectively used in humans for about 40 years. The glycoconjugates have substituted plain polysaccharide vaccines that have many limitations, especially in infants. The covalent linking of protein to carbohydrates has allowed to overcome T-cell-dependent type-2 response of sugars. Glycoconjugates can show improved responses (over plain saccharides) also in elderly and immunocompromised (and depending on the endpoint also in immunocompetent adults), but infants represent the main target of these vaccines because of their unique immune system. Differently from the plain polysaccharide vaccines, the glycoconjugates are also able to induce Immunoglobulin G (IgG) response in infants. Recently, vaccines containing conjugates directly expressed in Escherichia coli (bioconjugates) have been tested in the clinic against Shigella dysenteriae type 1, uropathogenic E. coli, and Streptococcus pneumoniae. Here, we report an overall comparison of classical- and bioconjugate vaccines in terms of the structural properties and the immunological response elicited. •Chemical conjugates are obtained by covalent coupling of polysaccharide to carrier protein.•Chemical conjugates are a very consolidated platform.•Bioconjugates are conjugates directly expressed in Escherichia coli.•Bioconjugates tested in clinic against Shigella dysenteriae, E.coli and S.pneumoniae.•Overall comparison of characteristics and immunological response of conjugate vaccines.