The protection of biological macromolecules, peptides, antibodies, proteins, and oligonucleotides is of extreme importance in biological, immunological and pharmacological applications. There is growing interest of PEG and its a- and w-substituted derivates and the protection offered by the covalent attachment of PEG to target molecules. PEGylation has become the method of choice for the delivery of bio-pharmaceuticals. Linear PEGs can offer one or two reactive groups that can bind with a functional group on the target molecule. PEGylation increases bioavailability, increases blood circulation of the target biomolecule/drug, shields receptormediated uptake by the reticuloendothelial system (RES), shields antigenic & immunogenic epitopes, prevents recognition and degradation by proteolytic enzymes, increases the apparent size of polypeptides, thus reducing the renal filtration & altering biodistribution, optimizes pharmacokinetics and decrease immunogenicity.