Polyethylene glycol (PEG), also called macrogol, is a polyether made up of ethoxy units often obtained by polymerizing the ring opening of ethylene oxide. PEG polymers are generally linear and have chemically active hydroxyl groups, facilitating conjugate formation with other functional groups. Thus, biomolecules and nanocarriers can form conjugates with PEG in a process called PEGylation. It is an approach employed by others to enhance the efficiency of drugs, vaccines, and gene delivery, and it is often utilized for cell and tissue targeting. It is a process of modification of the surfaces of particles, which usually occurs by adsorption, entrapment, or grafting of known polymer chain lengths of PEG. Incorporating PEG polymers into various nanocarriers improves the pharmacokinetic profile of drugs in the nanocarriers. PEGylation also enhances the diffusion of nanocarriers drug delivery systems across different biological systems, including the mucosal systems, extracellular spaces, and the brain. It also improves the physicochemical profiles of varying drug delivery systems and improves their biocompatibility by facilitating drug solubility and reducing their toxicity. PEGylated formulations have elongated residence in the body, enhanced drug stability, reduced metabolic enzymes-induced degradation, and minimized protein elimination. In this work, the process of PEGylation of different nanocarriers including lipid-based and polymeric nanoparticles, liposomes, and dendrimers will be explored. The applications of PEGylated nanocarriers in drug delivery will also be exhaustively discussed.