The focus in the field of biomedical engineering has shifted in recent years to biodegradable polymers and, in particular, polyesters. Dozens of polyester-based medical devices are commercially available, and every year more are introduced to the market. The mechanical performance and wide range of biodegradation properties of this class of polymers allow for high degrees of selectivity for targeted clinical applications. Recent research endeavors to expand the application of polymers have been driven by a need to target the general hydrophobic nature of polyesters and their limited cell motif sites. This review provides a comprehensive investigation into advanced strategies to modify polyesters and their clinical potential for future biomedical applications.