 PEgylation is a widely used drug delivery approach to improve the pharmacokinetics and pharmacodynamics of drugs by increasing their solubility, extending circulation time, and reducing immunogenicity. This technology has been applied to various therapeutic modalities and has led to over 30 clinically used PEgylated drugs with many more underclinical trials. The size, topology, and functionalities of PEg molecules utilized in these drugs have a significant impact on their performance. However, challenges remain in the development and clinical translation of PEgylated agents, including issues related to safety, efficacy, and cost-effectiveness. This article was authored by Yongshan Gao, Maitali Joshi, Zeng Mingjiao, and others.