Long-term oxygen therapy (LTOT) is a mainstay treatment for patients with severe resting hypoxemia secondary to chronic respiratory conditions including COPD. The evidence for LTOT is based on two trials that are now several decades old but have been insufficiently revisited. Therefore, many questions remain about precisely which patients experience the most benefit from LTOT, as well as how to define that benefit. Most studies have examined LTOT's effect on longevity rather than its impact on quality of life. In addition, many challenges exist in training both clinicians and patients on best practices for LTOT and associated equipment. Reimbursement policies have reduced the kinds of equipment available to the LTOT patient community, presenting additional challenges. This paper will review the current evidence for LTOT in COPD, the challenges involved with providing optimal therapy, and potential avenues of modernizing this essential intervention.