Nanocarriers hold immense potential for targeted drug delivery, but their therapeutic efficacy is often hindered by immunological interactions. The covalent attachment of polyethylene glycol chains, known as PEGylation, has emerged as a promising approach to modifying the immunological properties of nanocarriers. PEGylation offers several advantages, including steric stabilization, reduced protein adsorption, and decreased recognition by the immune system, resulting in prolonged circulation time and improved biodistribution. By shielding nanocarriers from immune recognition, PEGylation can mitigate undesired immune responses, such as rapid clearance by the mononuclear phagocyte system or induction of pro-inflammatory reactions. This chapter hereby highlights the nuances of the PEGylation technique while emphasizing the altered immunological properties of the PEGylated nanocarriers, which positively impact the various aspects of drug delivery.