Surgical site infections are a major contributor to morbidity and mortality in postsurgical care. Risk for surgical site infection is multifactorial and includes a host of microbial, patient-related, and procedure-related factors. Prevention of surgical infection relies on optimization of patient factors and use of a variety of evidence-based pharmacologic and nonpharmacologic measures. At the forefront of these measures is antimicrobial prophylaxis, which has been shown to be effective at reducing risk of surgical site infection. As guidelines for prevention of surgical site infection become increasingly complex and nuanced, surgical infection outcomes are increasing tied to quality outcome and performances measures.