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To provide information about hyperbaric oxygen therapy (HBOT), its mechanisms, indications and safe applications based on clinical evidence.This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care.After participating in this educational activity, the participant should be better able to:1. Recall the physiology of wound healing and the mechanisms of action of HBOT.2. Identify current applications of HBOT based on clinical evidence as well as its risks and contraindications.Treating chronic wounds and infections are challenging medical problems worldwide. Hyperbaric oxygen therapy (HBOT), the administration of 100% oxygen at pressures greater than 1.4 atmosphere absolute in a series of treatments, can be used as an adjunctive therapy in many wound care settings because it improves oxygenation and neovascularization and decreases inflammation in chronic wounds. A growing number of studies support the benefits of HBOT for enhancing wound healing and decreasing the likelihood of negative events such as amputation. However, many practitioners are unfamiliar with HBOT. This article provides a general introduction to HBOT, reviews the physiology and mechanisms of behind HBOT, discusses all the indications for HBOT, and explores in-depth the clinical evidence for HBOT in the treatment of arterial insufficiencies, diabetic ulcers, delayed radiation injury, and chronic refractory osteomyelitis.