Despite major advances in infection control and the ever-increasing use of broader-spectrum antibiotics in surgery, postoperative infections continue to occur under the best of care and in the best institutions. Postoperative infections, also termed surgical site infections (SSIs), can range from superficial wound infections to deep organ space infections. SSIs can be superficial and only require medical treatment (i.e. antibiotics), whereas others such as deep organ space infections resulting from an anastomotic leak can require multiple surgeries leading to sepsis and occasionally shock and death. Many if not most stakeholders in the field including surgeons, infectious disease specialists, infection control nurses, etc., in general, advocate the use of prophylactic antibiotics and the enforcement of greater levels of sterility, reasoning that all postoperative infections must arise from some type of direct contamination event. In this article, the alternative view is presented that today, in the era of mandated asepsis protocols, enhanced recovery programs, and enforcement of prophylactic antibiotics in all cases, many if not most postoperative infections and SSIs occur from pathogens endogenous to the patient and not from sources exogenous to the patient. It is also suggested that applying broader antibiotic coverage in elective surgery is neither an evolutionarily stable strategy nor inexorable in the context of emerging knowledge in the field of gut ecology. Here this concept is reviewed and the rationale behind using agents that preserve the gut microbiome and attenuate pathogen virulence in lieu of applying broader-spectrum antibiotics and greater levels of sterility.