Hyperbaric oxygen (HBO2) is the inhalation of 100% oxygen at pressures > 1.4 times atmospheric pressure. Hyperbaric oxygen can be delivered in monoplace (single person) or multiplace (multi-person) chambers. Most clinical HBO2 exposures are between 2 and 2.4 atm abs for approximately 2 hours. Hyperbaric oxygen causes the blood and tissue oxygen levels to increase, reduces the volume of intravascular and tissue bubbles (to treat decompression sickness [DCS] and arterial gas embolism [AGE]), and accelerates wash-out of other gases, such as nitrogen or carbon monoxide (CO), which is important for DCS, AGE, and CO poisoning. Hyperbaric oxygen favorably modulates ischemia-reperfusion injury by transiently inhibiting neutrophil-endothelial interactions, which is important for patients with DCS, AGE, CO poisoning, and potentially other acute ischemic conditions. Because of enhanced oxygen delivery, HBO2 is used for acute crush injury, ischemic flaps and grafts, acute central retinal arterial occlusion, other acute arterial occlusions, and idiopathic sudden sensorineural hearing loss. Hyperbaric oxygen has antimicrobial effects and is offered for patients with limb- or life-threatening infections, such as clostridial gas gangrene and necrotizing fasciitis. The most common US indication for HBO2 is the treatment of ischemic wounds (eg, diabetic lower extremity wounds, late effects of radiation, and refractory osteomyelitis). In ischemic wounds, HBO2 can deliver sufficient oxygen to the nonhealing wound to stimulate angiogenesis and healing through multiple mechanisms, including increased collagen production, increased growth factor receptor numbers, upregulation of vascular endothelial growth factor, increased circulating endothelial progenitor cells, and improvement in neutrophil-mediated host defense. Clinical trials support efficacy of HBO2 for acute CO poisoning, diabetic lower extremity wounds, crush injury, and radiation necrosis. Most hyperbaric chambers are associated with wound care centers and may be hospital based or nonhospital based. We review some of the disorders treated with HBO2 that hospital-based clinicians may be asked to evaluate.