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Oxygen at high doses or under pressure should be viewed as a drug with its own set of toxicities as well as drug interactions.  Hyperbaric oxygen therapy is oxygen administered at both elevated doses and elevated pressures. Hyperbaric oxygen therapy is 100% oxygen administered at one and a half to three times the atmospheric pressure at sea level. It is used to treat a variety of different conditions including but not limited to carbon monoxide poisoning, decompression sickness, arterial gas embolism, radiation-induced tissue injury, necrotizing fasciitis, osteomyelitis, problem wounds, thermal burns, etc. Untreated pneumothorax remains the only absolute contraindication to hyperbaric oxygen treatment. However, there are many drugs with a side effect profile that could be exacerbated by hyperbaric oxygen, and the relative contraindications of chemotherapeutic drugs with hyperbaric oxygen therapy will be the focus of this article. Hyperbaric oxygen therapy is frequently used in the treatment of post-radiation injuries, and many of these patients have also undergone chemotherapy as a part of their treatment regimen, raising the concern for potential side effects with hyperbaric oxygen. A careful review of current and past medications is important when deciding to treat with hyperbaric oxygen—three drugs to evaluate include bleomycin sulfate, doxorubicin, and cis-platinum (cisplatin).