In some instances, oxygen therapy may negatively affect a patient's condition. Because oxygen may cause blood vessels to constrict, it may reduce circulation in areas far away from the heart and increase the risk of stroke. Some individuals with COPD may actually have their condition worsen when given oxygen therapy. Hyperbaric oxygen therapy may cause a serious and life threatening type of seizure called a grand mal seizure.

Oxygen therapy is not advisable in individuals with severe airflow limitation, who continue to smoke cigarettes, who have not yet received other therapies, or who are not sufficiently motivated to adhere to safety precautions.

Oxygen therapy should always be administered by a qualified healthcare provider.

Inhalation: There are numerous studies showing the effectiveness of inhaling oxygen. The U.S. Food and Drug Administration (FDA) has approved oxygen therapy as a treatment for a number of conditions, in both emergency and non-emergency circumstances, including non-healing wounds (post-surgical or diabetic), radiation induced soft tissue death and osteonecrosis (death of bone tissue), flesh eating bacteria, carbon monoxide poisoning, decompression sickness, acute arterial ischemia (crush injury, compartment syndrome), compromised skin grafts or flaps, severe infection by anaerobic bacteria (such as gas gangrene), air or gas embolism, and severe uncorrected anemia (low red blood cell count resulting in fatigue and weakness) when blood transfusion is not available (not available or blood transfusion forbidden for religious reasons).

By mouth: Vitamin O supplements, composed largely of salt water and "stabilized" or "aerobic" oxygen, have been purported to cure or prevent serious diseases such as cancer, heart disease, and lung disease and to enrich the bloodstream with supplemental oxygen. Proponents of vitamin O claim that disease occurs because the body is lacking in oxygen. It is therefore believed that by ingesting oxygen via vitamin O supplements, various ailments may be reversed. There is currently insufficient available clinical evidence to support the use of vitamin O supplements for any indication.

Oxygen is almost always delivered in the form of a continually flowing gas. The duration of oxygen therapy varies according to the medical condition of the patient. For instance, patients with carbon dioxide poisoning or decompression sickness may only receive oxygen for a short period of time, whereas individuals with certain kinds of diabetic wounds or a chronic eye condition may receive oxygen on a regular basis. Some individuals, such as those with the lung condition chronic obstructive pulmonary disease (COPD), may require oxygen therapy for the rest of their lives.

A variety of different machines and devices are used to administer oxygen therapy, including tubes that go into the nose, a face mask, an anesthetic machine, and specialized masks such as flight masks. Hyperbaric pressure therapy is usually given in a small chamber. Bag-valve-masks require that the individual squeeze the device to deliver the oxygen.

Oxygen is contained and transported in a number of ways. Specialized types of cylinders may be less stable, but they hold more oxygen because oxygen is compacted until it is ready to be used. In general, oxygen cylinders need to be refilled. Oxygen concentrators are larger than oxygen cylinders, remove oxygen from the surrounding air to purify it, and do not need to be refilled.

Some individuals may need to enter a special room or chamber to inhale oxygen. In these cases, the oxygen is not stored in the room, but pumped in. This is usually the case on airplanes and in hyperbarotric oxygen therapy. Oxygen therapy may also be given in an individual's room in their home.

Oxygen is an element essential to human life, and has been referred to as "vitamin O," even though it is not a true vitamin.

Taking oxygen as a "vitamin O" supplement is a practice not endorsed by any major medical organization. There appears to be two types of vitamin O products available on the market. The first is an expensive health supplement that is composed largely of salt water and "stabilized" or "aerobic" oxygen, and is marketed under many different brand names. Companies, such as RGarden have advertised vitamin O (without germanium) as a purported cure or preventive agent for serious diseases such as cancer, heart disease, and lung disease. It has also been claimed that when taken by mouth, vitamin O supplements may enrich the bloodstream with supplemental oxygen. The second vitamin O product currently available contains the element germanium, which when synthetically derived has been said to be potentially nontoxic and safe at high doses. The various health claims for use of vitamin O have not been substantiated with scientific evidence. However, numerous product testimonials mention the effects of vitamin O on a variety of conditions.