PEGylation, the attachment of polyethylene glycol (PEG) to proteins, is currently main technology for improving efficacy of protein drugs. This technology can prolong the plasma half-life, augment the in vivo stability, and diminish the immunogenicity of therapeutic proteins. Therefore, PEGylated proteins have the enhanced therapeutic efficacy and the reduced undesirable effects versus their native therapeutics. Since the first PEGylated protein product appeared on the market in the early 1990s, currently ten PEGylated protein products have been launched. These marketed drug products have proved the applicability and safety of the PEGylation technology. This review presents overview of PEGylation technology and addresses characteristics of PEGylation methods applied for the development of several protein drugs.