The noble gases have always been an enigma. Discovered late in the history of chemistry and in seemingly small quantities in our atmosphere, they are some of the most unreactive elements known. However, despite being extremely inert, the noble gases (helium, neon, argon, krypton, xenon and radon) have found diverse and ever expanding applications in medicine. Of all of them, the gases that have found the greatest number of uses in the field of anaesthesia and related specialties are helium and xenon. This review focuses on the history of the discovery of both gases, their unique physicochemical properties and describes their uses in clinical practice with particular emphasis on those applicable to anaesthesia.