The noble gas xenon has been known for >50 years in the field of anesthesia with an emerging series of favorable features; several clinical and preclinical studies performed over the last years reveal a renewed interest because they substantially agree on attributing relevant analgesic properties to xenon. The main mechanism of action is the inhibition of N-methyl-d-aspartate receptors of glutamate; it involves the blocking of painful stimuli transmissions from peripheral tissues to the brain and it also avoids the development of pain hypersensitivity. Therefore, this mechanism is responsible for the inhibition of pain transmission at spinal and supraspinal levels, as well as the cortical level. In all these levels of pain pathways, as the development of hyperalgesia is possible, xenon efficacy can also be based on the blocking of these processes. Several forms of pain share such mechanisms in their maintenance, and xenon can be successfully used at low dosages, which have no effects on vital parameters. The literature shows that analgesic features could also emerge outside the field of anesthesia; thus, this could permit xenon to have a larger usage according to local availability.