Despite considerable research effort there is little controlled evidence that a course of hyperbaric oxygen therapy (HBO2T) results in any benefit for patients with multiple sclerosis (MS). The great majority of randomized trials involved investigating a course of 20 treatments at pressures between 1.75 and 2.5 atm abs daily for 60-120 min over 4 wk against a placebo regimen. None has tested the efficacy of HBO2T against alternative current best practice. A systematic review of this randomized evidence suggests there is no significant benefit from the administration of HBO2T (Improved EDSS after HBO2T: OR = 2.02, 95% CI 0.63-6.43. Improved sphincter function: OR = 1.3, 95% CI 0.8-2.11). On average, 42 patients would need to be treated before we could expect one individual to benefit with an improved disability status score; however, we cannot be confident that the number we would need to treat is less than infinite (NNT = 42, 95% CI 15 to infinity). There is some case for further investigation of possible therapeutic effects in selected sub-groups of patients and for the response to prolonged courses of HBO2T at more modest pressures; however, the case is not strong. At this time, we cannot recommend the routine treatment of MS with HBO2T.