The emergence of antibiotic resistance in microbial strains is representing one of the major threats to public health worldwide, due to the decreased or total cancelling of the available antibiotics effectiveness, correlated with the slow development of novel antibiotics. Due to their excellent biodegradability and biocompatibility, the synthetic polymers could find a lot of biomedical applications, such as the development of biomaterials with optimized properties and of drug delivery systems. This review is focusing on the applications of synthetic, biodegradable polymers for the improvement of antiinfective therapeutic and prophylactic agents (i.e., antimicrobial and anti-inflammatory agents and vaccines) activity, as well as for the design of biomaterials with increased biocompatibility and resistance to microbial colonization.