Xenon is a monatomic gas that belongs to the family of noble gases. Like other noble gases, it is characterized by a filled valence shell and therefore exhibits low chemical reactivity. Paradoxically, xenon possesses a remarkable spectrum of biological effects that are of potential clinical interest. Xenon is an approved anesthetic drug with analgesic properties. In addition to that xenon is neuroprotective in preclinical models of focal and global brain ischemia, spinal cord ischemia and traumatic brain injury. These neuroprotective effects are generally observed at concentrations of xenon ranging from 35 to 75%. Although the activation of ATP-sensitive potassium channels or of two-pore potassium channels may explain some of the neuroprotective effects of xenon, the noble gas appears to work primarily by limiting the overstimulation of N-methyl-D-aspartate (NMDA) glutamate receptors under excitotoxic stress conditions. More specifically, xenon has been reported to compete with glycine, a co-agonist for NMDA receptor activation. Excitotoxic stress mediated through NMDA receptors is most generally associated to acute central nervous system insults such as ischemia and traumatic brain injury, but chronic, low-level overexcitation of these receptors is also a possible contributor to neuronal death in a number of chronic neurodegenerative conditions, including amyotrophic lateral sclerosis, Parkinson's disease and Alzheimer's disease (AD). The implication of excitotoxic stress in AD-mediated neurodegeneration is specifically supported by studies reporting the benefits of treatments with NMDA receptor antagonists in preclinical models of the disease. Of interest, one of these antagonists memantine has also a small beneficial effect on cognitive impairment in AD patients.