Necrotizing skin and soft tissue infections are caused by many different bacteria, are frequently polymicrobial, and may have a deceptively innocent early clinical presentation. Clostridial and nonclostridial necrotizing infections are frequently similar in their early presentation. The initial presentation of these infections can be insidious, which results in delay in diagnosis and the start of therapy. The clinician must use sound medical principles of clinical history and meticulous examination in each patient, combined with constant suspicion, to establish a timely diagnosis. This group of infectious diseases is associated with frequent morbidity and significant mortality rates, which increase with any delay in the diagnosis and the initiation of medical and surgical therapy. Also associated with these necrotizing infections is an excessive index of litigation. This review is intended as a guide for the clinician in making an early diagnosis of any necrotizing skin and soft tissue infection and initiating effective medical and surgical therapy.