Polymer conjugation, especially by poly(ethylene glycol), has become a leading technology for the delivery of proteins. Nowadays, biotech drugs represent an increasing share of the new approved drugs, but their use is often prevented by drawbacks and safety concern. In particular, short in vivo half-life and immunogenicity are significant problems faced by the researchers dealing with the development of protein and peptide drugs. The chemical linking of a polymer to the protein surface has proved effective in prolonging protein blood circulation and reducing the immunogenicity by decreasing renal clearance and shielding immunogenic epitopes, respectively. So far, PEGylation has already led to nine marketed conjugates with great therapeutic success.