A primary concern in healthcare today is the prevention of infection. Surgical site infections (SSIs) are the leading type of infection among hospitalized patients. Advanced practice nurses play a vital role in patient care, and those who incorporate best practice standards can reduce the morbidity and mortality associated with SSIs. The Centers for Disease Control and Prevention have published recommendations for prevention of SSIs. This article reviews current literature regarding the prevention of SSIs and how critical care practitioners can incorporate these scientifically tested recommendations into their practice.