Hyperbaric oxygen therapy (HBOT), the administration of pressurized 100% oxygen, is used as an adjunct to aid healing in selected chronic wounds. Though the therapy has had a controversial history, research is now elucidating the mechanisms by which HBOT helps to heal wounds. HBOT increases growth factors and local wound signaling, while also promoting a central stem cell release of endothelial progenitor cells from the bone marrow via nitric oxide pathways. The clinical data continue to accumulate in support of HBOT to help hasten wound healing, and reduce the amputation rate in diabetic ulcers. In appropriate patients, HBOT is an effective, noninvasive, adjunct modality that can be used to hasten chronic wound healing.