Necrotizing soft-tissue infections are rapidly spreading bacterial infections that account for a relatively small proportion of infections, but are aggressive in nature and nearly uniformly fatal if left untreated. Prompt recognition, antibiotic therapy, aggressive surgical debridement, and hyperbaric oxygen (HBO) therapy have reduced the mortality resulting from these infections. Oxygen, at increased pressures, augments tissue oxygen partial pressure, allowing increased bacterial killing by providing substrate for the formation of oxygen free radicals and augmenting respiratory burst. During the healing process, hyperoxia causes increased formation of capillaries for oxygen, nutrient, and antibiotic delivery, leading to increased efficacy of some antibiotics in the high oxygen environment, and possibly more rapid overall wound healing. Although there are no randomized trials of HBO in these infections, in vitro data and meta-analysis of clinical cases strongly support the use of HBO.