Nanoparticles (NPs) are crucial in the emerging field of nanomedicine due to their unique interactions with matter. Polyethylene glycol (PEG) is commonly used to coat NPs to reduce their interaction with the immune system and increase their circulation time in the body. This article provides an introduction to PEGylation, a process that involves coating NPs with PEG to enhance their stealth properties and improve their performance in imaging and therapy applications. Key considerations for designing PEGylation protocols include the type of NP, PEG length, conformation, and characterization methods. PEGylation can significantly improve NP circulation time, reduce nonspecific binding, and enhance targeting efficiency. However, challenges such as aggregation, toxicity, and degradation must be addressed to fully realize the potential of PEGylated NPs. The article also discusses alternative materials and strategies for improving NP performance, highlighting the ongoing research and development in this field.Nanoparticles (NPs) are crucial in the emerging field of nanomedicine due to their unique interactions with matter. Polyethylene glycol (PEG) is commonly used to coat NPs to reduce their interaction with the immune system and increase their circulation time in the body. This article provides an introduction to PEGylation, a process that involves coating NPs with PEG to enhance their stealth properties and improve their performance in imaging and therapy applications. Key considerations for designing PEGylation protocols include the type of NP, PEG length, conformation, and characterization methods. PEGylation can significantly improve NP circulation time, reduce nonspecific binding, and enhance targeting efficiency. However, challenges such as aggregation, toxicity, and degradation must be addressed to fully realize the potential of PEGylated NPs. The article also discusses alternative materials and strategies for improving NP performance, highlighting the ongoing research and development in this field.