Drug and protein delivery techniques and methods, which, in most cases, are concurrently investigated from the very time a new molecular entity is proposed, have become valuable tools for the development of numerous therapeutic molecules. Attracting the attention of academia and industrial researchers, several polymer conjugation methodologies have been shown to have a wide range of applications and a success rate that have been confirmed by the numerous conjugates already in clinical use or under investigation in on-going clinical trials. Having attained a high level of sophistication, this technology is able to generate homogeneous conjugates by exploiting specifically designed coupling strategies (based, for example, on the use of enzymes), which ensure good product characterization, high activity retention, and batch-to-batch reproducibility. Poly(ethylene glycol) (PEG), which is the current gold standard for stealth polymers in the emerging field of polymer-based drug delivery, is in competition with other polymers that have convenient features such as biodegradability. PEG still holds first place as far as PEGylated derivatives under investigation in clinical trials are concerned, and it will presumably remain the polymer of choice even in the future as further improvements such as the development of new copolymers based on PEG or PEG derivatives will overcome for example the hurdle of biodegradability.