The current review presents an update on polyethylene glycol (PEG), which is widely used as a covalent modifier of macromolecules. This review discusses the polymers suitable for conjugation, their conjugation methods, and their properties. Proteins and bioactive substances can be chemically modified by binding synthetic macromolecules of PEG to the surface of these biomolecules. Protein and peptide PEGylation improves the biopharmaceutical properties of drugs-that is, increased stability, increased resistance to proteolytic inactivation, decreased to nonexistent immunogenicity, increased circulatory lives, and low toxicity. These altered properties improve the delivery and efficacy of proteins.