The spectrum of severe soft-tissue surgical infections extends from synergistic necrotizing soft-tissue infections to histotoxic clostridial infections. These syndromes may demonstrate dramatic destruction of underlying tissue far out of proportion to the external evidence for infection, although a marked systemic response in common. The differential diagnosis hinges on the clinical presentation, the Gram's stain, and operative inspection. More important than the precise label placed on a given case is the early recognition of the urgent surgical nature of the infection. Signs indicating a rapidly spreading soft-tissue infection mandate fluid resuscitation, broad-spectrum antibiotics, and early operative exploration with aggressive debridement. These are highly lethal infections in which timely recognition and effective management may be lifesaving.