Postoperative sepsis is a major cause of surgical associated morbidity and mortality. Our goal is to describe its incidence, pathophysiology, and contributing factors. In addition, we will review preventive measures and treatment options that may possibly reduce its healthcare burden.We review epidemiologic data and clinical tools presented in multiple current studies, which may help lower incidence and improve outcome of postoperative sepsis.The incidence of postoperative sepsis has not declined over the past years, although mortality is trending downwards. Several biochemical and genetic markers may allow early diagnosis. Prevention and prompt treatment may lower mortality.