The coating of the exterior of nanocarriers with polyethylene glycol (PEG; known as “PEGylation”), has emerged as one of the most widely adopted approaches to impart stealth properties to pharmaceutical nanocarrier systems. The PEGylation tactic offers a stealth barrier towards the adsorption of circulatory proteins owing to its hydrophilicity, elasticity, neutralization, and hydration properties. PEGylation dramatically provides sustained drug release benefits, reduces immune sensitivity, as well as improves the systemic circulation period, Overall, PEGylation effectively improves the therapeutic efficacy of the loaded therapeutic moiety in treating target cells and tissues. This chapter offers discussion on drug delivery nanosystems that are developed based on the principle of PEGylation strategy. Furthermore, a detailed account of the pharmaceutical and biomedical applications of PEGylated nanocarriers has also been presented in detail.