The treatment of delayed radiation injuries (soft tissue and bony radiation necrosis) is one of thirteen conditions approved by the Hyperbaric Oxygen Therapy Committee of the Undersea and Hyperbaric Medical Society as appropriate indications for hyperbaric oxygen (HBO2). This paper provides a systematic review of the literature reporting the results of HBO2 therapy in the treatment and/or prophylaxis of delayed radiation injury. Since the introduction of the concept of evidence based medicine, the medical community in general has set out to apply more critical and stringent standards in evaluating published support for therapeutic interventions. Evidence based medicine is designed to discover the best evidence available and apply it in daily practice for treatment of the individual patient. The preferred level of evidence is the randomized controlled trial, however, other evidence has merit as well. In this review, seventy-four publications are represented reporting results of applying HBO2 in the treatment or prevention of radiation injuries. These are appraised in an evidence-based fashion by applying three established systems of evaluation. All but seven of these publications report a positive result when HBO2 is delivered as treatment for or prevention of delayed radiation injury. These results are particularly impressive in the context of alternative interventions. Without HBO2, treatment often requires radical surgical intervention, which is likely to result in complications. Other alternatives including drug therapies are rarely reported, and for the most part have not been the subject of randomized controlled trials. Based on this review, HBO2 is recommended for delayed radiation injuries for soft tissue and bony injuries of most sites. Of note, an increasing body of evidence supports HBO2 for radiation-induced necrosis of the brain. For other radiation-induced neurological injuries, additional study is required before recommendations for routine hyperbaric therapy can be made.