This chapter discusses necrotizing soft tissue infections (NSTIs). A typical scenario will be a patient presenting to the emergency department with local signs of soft tissue infection and sepsis, but an NSTI may also involve a recent surgical site or a chronically ill, hospitalized patient. Frequent findings on history and physical exam of patients with NSTIs are discussed, as well as differential diagnoses, workup, treatment, outcomes, complications, common curveballs, and clean kill questions pertinent to the oral boards.