Hyperbaric oxygen therapy involves intermittent inhalation of 100% oxygen under a pressure greater than 1 atm. Despite over a century of use in medical settings, hyperbaric oxygen remains a controversial therapy. The last 20 years have seen a clarification of the mechanism of action of hyperbaric therapy and a greater understanding of its potential benefit. However, despite the substantial evidence that hyperbaric oxygen may have a therapeutic effect in certain carefully defined disease states, many practitioners remain unaware of these findings or are concerned about using hyperbaric therapy because of the controversy it has engendered. This review examines the indications currently considered appropriate for hyperbaric oxygen and briefly evaluates animal and clinical data substantiating these indications. Areas in which the mechanism of action of hyperbaric oxygen is still not well understood, as well as possible new areas of applications, are discussed.