The attachment of linear polyethylene glycol (PEG) to peptides and proteins for their stabilization for in vivo applications is a milestone in pharmaceutical research and protein–drug development. However, conventional methods often lead to heterogeneous PEGylation mixtures with reduced protein activity. Current synthetic efforts aim to provide site-specific approaches by chemoselective targeting of canonical and noncanonical amino acids and to improve the PEG architecture. This synopsis highlights recent work in this area, which also resulted in improved pharmacokinetics of peptide and protein therapeutics.