Glycosylation is the one of the most challenging post-translational modifications. It usually has a set of modifications instead of a single modification. Even a single glycosylated site on a peptide may have a number of glycan isoforms with different chain length and branches attached. O-glycans attach to a polypeptide mainly through a glycosidic bond between the terminal monosaccharide residue and the OH group of Serine or Threonine. Unlike N-glycans, there is no known O-linked amino acid consensus sequence yet. The O-glycans are structurally diverse. They can be divided into several structural families with relatively heterogeneous core structures.