Chronic respiratory conditions are responsible for increasing numbers of patients in need of long-term oxygen therapy (LTOT). However, many patients do not use their oxygen as prescribed. Unless we can assist these patients in living with oxygen therapy, optimal clinical outcomes will not be achieved. We conducted a meta-synthesis of qualitative research studies. We included any qualitative study that focused on the psychosocial nature or experience of patients prescribed LTOT. Four research studies met the conditions of our search. We performed a rigorous methodological protocol for meta-synthesis as described by the Joanna Briggs Institute. A total of 12 findings formulated four themes. These themes included the following: adapting oxygen to life's circumstances, living in a restricted world, self-management is fostered by oxygen, and submission and dependency. From the four thematic categories established, meta-synthesis resulted in two major results: persons prescribed oxygen rationalize its use while negotiating lifestyle interference and physical restrictions and the drive to care for one's self is conflicted. This meta-synthesis showed that each oxygen user faces tremendous physical, psychological, and emotional challenges. They strive to adapt and maintain mastery but eventually oxygen dependency results. These challenges affect the patient's ability to adhere to their treatment guidelines. These barriers and challenges are seldom addressed and are under-treated. Clinicians involved in LTOT need to be aware and work with the patients to facilitate their use of oxygen. Inclusion of the patients' perspective can guide practice and assist with the development of new interventions and management strategies.