While recompression and hyperbaric oxygen administration remain the mainstays of treatment for decompression illness (DCI), drugs that might improve outcomes or prove beneficial in first aid management have been sought. There has been much interest in lidocaine, a sodium channel-blocking agent used clinically as an antiarrhythmic and local anesthetic. The relevant literature is reviewed. Lidocaine is neuro-protective in cerebral arterial gas embolism (CAGE) in vivo, and in a variety of in vivo and in vitro models of ischemic brain injury. There has been limited in vivo investigation of efficacy in DCI where bubbles have formed from dissolved nitrogen. Mechanisms of neuro-protection by lidocaine include deceleration of ischemic ion fluxes across the neuronal cell membrane and prevention of the consequent neurotoxic events. In addition, lidocaine lowers neuronal metabolism, exerts advantageous effects on cerebral hemodynamics, and is a potent anti-inflammatory. There is one randomized double blind study that demonstrates improved neuropsychological outcomes in cardiac surgery patients receiving lidocaine. Clinical evidence of efficacy in DCI is limited to anecdotal reports. Expeditious administration of lidocaine is justified in cases of unequivocal CAGE. Speculative use may be justified in severe neurologic DCI after patient counseling and consent.