In this chapter, we outline the protocols for PEGylation of some drug carriers, such as dendrimer, polymeric nanoparticles, liposomes, for systemic delivery. PEGylation simply refers to the modification of particle surface by covalently grafting, entrapping, or adsorbing PEG chains of vivid length. However, limitation of simple adsorption being easy displacement of the coating layer in vivo, covalent mode for PEGylation of nanoparticles is mostly preferred, and outlined herein. Derivatization and activation of polyethylene glycol is an important step during PEGylation and its chemistry chiefly relies on availability as well as type of functional groups on carrier periphery. A summarized set of protocols for PEGylation of widely explored nanocarriers for systemic delivery is presented.