Oxygen was first identified at the end of the eighteenth century but was not used as a therapeutic tool until 1887, by Holsapel. Although oxygen toxicity has been reported, tolerance of long-term oxygen therapy (LTOT) is excellent. In 1979, for the first time, Neff and Petty observed that LTOT increased life expectancy. In the early 1980s two randomized studies (the NOTT and the MRC trial) established the clinical and hemodynamic benefits of LTOT, and their findings were later supported by other studies; recently, however, it has been noted that the hemodynamic benefits do not last more than two years. Polycythemia and neuropsychological functions have also been found to improve with LTOT. Quality of life seems to be affected in females but not in males. A first attempt to establish recommendations for LTOT was made at the Denver meeting in 1987, and this was followed by the publication of more guidelines by lung societies in various countries. In addition to the classic nasal prongs and facial masks, new oxygen delivery devices allowing a 50% oxygen saving were introduced: the transtracheal catheter and the nasal cannula with reservoir and oxygen-conserving valve, which combined with liquid oxygen, increased patients ambulatory activities (including traveling) and improved hemodynamic parameters. Gray areas of LTOT include nocturnal or diurnal desaturation during effort but with daily Pa02 > 60 mm Hg at rest.