Patients with severe diabetic foot ulcerations that fail to heal with standard conventional therapies may be candidates for hyperbaric oxygen therapy; these patients also should be evaluated for atypical wound etiologies. Medical evaluation includes thorough history, physical examination, screening laboratory tests, and ulcer biopsy. During hyperbaric oxygen therapy, patients breathe 100% oxygen at 2 times to 3 times atmospheric pressure while enclosed in a hyperbaric chamber. Over time, administration of hyperbaric oxygen therapy can result in wound neovascularization and enhanced limb salvage. In patients with suspected atypical ulceration, referral to a multidisciplinary wound healing center is considered standard of care.