Hospital-acquired infections arising from implanted polymeric medical devices continue to pose a significant challenge for medical professionals and patients. Often times, these infections arise from biofilm accumulation on the device, which is difficult to eradicate and usually requires antibiotic treatment and device removal. In response, significant efforts have been made to design functional polymeric devices or coatings that possess antimicrobial or antifouling properties that limit biofilm formation and subsequent infection by inhibiting or eliminating bacteria near the device surface or by limiting the initial attachment of proteins and bacteria. In this Viewpoint, we highlight the magnitude of device-associated infections, the role of biofilm formation in human pathogenesis, and recent advances in antimicrobial and antifouling polymers, as well as current strategies employed in commercial devices for preventing infection.