Oxygen is widely used for a variety of medical and surgical disorders even in the absence of demonstrable fall of arterial PaO2. For acute myocardial infarction, oxygen may prove useful to improve cardiac muscle and tissue oxygenation and relieve breathlessness. Its use in uncomplicated myocardial ischemic episodes is largely supplemental. It is an important constituent of therapy for acute decompensation of heart failure. Nocturnal domiciliary oxygen therapy has shown to improve quality of life and sleep disordered breathing in chronic heart failure. In neurological diseases, use of supplemental O2 for acute stroke is unconvincing but significant benefit is demonstrable in about 75 percent of patients of cluster headaches. Oxygen has no beneficial role for diseases characterized by problems of oxygen transport (severe anemias and hemoglobin abnormalities) except in acute conditions such as for anemia following massive bleeding or intravascular hemolysis, acute met hemoglobinemia following toxic exposure to drugs and chemicals, acute sickle cell crisis and carboxyhemoglobinemia resulting from acute carbon monoxide poisoning. The later condition is one of the absolute indications for hyperbaric oxygen therapy. Supplemental oxygen therapy is employed for a number of other conditions such as hypovolemia, sepsis, peri and post-operative care especially in the presence of risk factors and or pre-existing lung disease. It has an important role in palliative care of breathlessness from advanced cancers and end-stage diseases.