Bacterial resistance to available antibiotics has resulted in enhanced efforts at antibiotic stewardship but also has led to investigation into alternative methods for managing surgical infections. Antimicrobial peptides (AMPs) are naturally occurring compounds produced by all prokaryotic and eukaryotic cells that have potential as an alternative to conventional antibiotics.The published literature was reviewed for investigations that were relevant to infections commonly seen by surgeons and the potential applicability of AMPs for surgical care.Antimicrobial peptides are low-molecular-weight peptides with activity against bacteria, fungi, and viruses. Experimental evidence shows that AMPs have activity against highly resistant bacteria identified from human infections. Furthermore, these peptides can be designed as semi-synthetic or totally synthetic constructs for potential clinical use. Antimicrobial peptides appear to have in vivo activity in limited animal studies, but the experimental models for evaluation of these peptides need more clinical relevance. These products are in clinical evaluation at present but are limited in number and are being evaluated primarily for topical applications.Antimicrobial peptides have considerable in vitro evidence that supports their use for the prevention and treatment of surgical infections. Better experimental and clinical trial efforts are needed to move this technology toward applicability in surgical care.