Synthetic polymers have transformed society in many areas of science and technology, including recent breakthroughs in medicine. Synthetic polymers now offer unique and versatile platforms for drug delivery, as they can be “bio-tailored” for applications as implants, medical devices, and injectable polymer-drug conjugates. However, while several currently used therapeutic proteins and small molecule drugs have benefited from synthetic polymers, the full potential of polymer-based drug delivery platforms has not yet been realized. This review examines both general advantages and specific cases of synthetic polymers in drug delivery, focusing on PEGylation in the context of polymer architecture, self-assembly, and conjugation techniques that show considerable effectiveness and/or potential in therapeutics.