A suitable glycan structure is required for optimal protein-based therapeutics, such as antibody-dependent cell cytotoxicity in therapeutic antibodies, enzyme replacement therapy for lysosomal diseases, and controlled clearance of cytokines from the blood. Expressing proteins in unicellular organisms such as bacteria and yeast would be commercially advantageous compared with mammalian cells if these organisms could be engineered to produce human-type glycans. Although using bacteria and yeast to produce humanized glycoproteins and to conduct glycan remodeling of proteins remain a long-term goal for microbiologists and biochemists, recent studies in the field of microbial glycobiology in combination with synthetic chemical techniques suggest that this dream is close to being realized.