Polyethyleneglycol (PEG) compounds have a large hydrogen bonding capability and possess various functions that depend on the length of the chain and conformational diversity. Modification of a drug with PEG is a well-known technology for improving the physicochemical properties and biological responses of a drug. There are many reports about the modification of small molecules with PEG, however, there are no modified small molecule products currently on the market. Several protein products for medical use are commercially available. In this review, the effects of modification with PEG on biopharmaceuticals are described through the comparison of two interferon-α products modified with PEG, one with 12 kDa linear PEG and the other 40 kDa branched PEG. There is one original drug delivery system product, Doxil(®)/Caelyx(®), on the market in which liposomes modified with PEG and encapsulating doxorubicin are stabilized sterically and invisible to the reticuloendothelial system. The benefits of modification with PEG are described here with examples of modified products on the market and used in clinical trials.