Bacterial resistance to antibiotics is a growing problem and has made it necessary to resort to antibiotics that have considerable toxicities. We reasoned that targeted delivery of an antibiotic to the site of infection would result in increased anti-bacterial activity, and the lower dosing made possible by the targeting would reduce side effects. To test this concept, we set out to explore peptide-based targeting on infections. We used phage display on Staphylococcus aureus bacteria and in vivo screening in mice to identify peptides that would recognize S. aureus-infected tissue. A cyclic 9-amino acid peptide identified from the screening bound to S. aureus bacteria in vitro and selectively accumulated in vivo in S. aureus-infected lungs and skin in mice. The peptide significantly enhanced the accumulation of intravenously injected nanoparticles loaded with vancomycin in the site of infection, thus more effectively suppressed Staphylococcal infections than free vancomycin.