Long-term oxygen therapy (LTOT) is the cornerstone mode of treatment in patients with severe chronic obstructive pulmonary disease (COPD) associated with resting hypoxaemia. When appropriately prescribed and correctly used, LTOT has clearly been shown to improve survival in hypoxemic COPD patients. Adherence to LTOT ranges from 45% to 70% and utilization for more than 15 hours per day is widely accepted as efficacious. Although several studies have addressed the level of patients' adherence to LTOT, few have suggested or evaluated interventions that conduce to compliance enhancement. The lack of sufficient data regarding COPD patients following oxygen prescription is an enormous void that must be duly confronted to augment clinical effectiveness and cost containment for the long term use. The present review article highlights factors influencing the compliance of patients using LTOT and emphasizes novel strategies and interventions that may prove to be of significant benefit given the remarkably little current research appraising this issue. Therefore, additional research should be promptly performed to verify the efficacy of newly designed approaches in improving the outcomes of patients receiving LTOT. 1. Introduction It is well established that long-term oxygen therapy (LTOT) is the only therapeutic modality proven to alter the late course of chronic obstructive pulmonary disease (COPD). Particularly, two landmark studies, the Nocturnal Oxygen Therapy Trial (NOTT) and the British Medical Research Council (MRC) conducted in the late 1970s have explicitly demonstrated that LTOT (when used for more than 15？hours/day) improves survival rates in patients with severe COPD associated with resting hypoxemia [1, 2]. In terms of maximum benefit, continuous oxygen administration (≥15？h/d) is superior to intermittent or nocturnal use [3]. There is also accumulating evidence that LTOT has favourable effects on other outcome measures, including depression, cognitive function, quality of life, exercise capability, and frequency of hospitalization [4–10]. Moreover, it stabilizes and sometimes reverses the progression of pulmonary arterial hypertension and it diminishes as well cardiac arrhythmias and electrocardiographic findings indicative of myocardial ischemia [11, 12]. The effectiveness of LTOT in improving survival has been substantiated only in stable COPD patients with severe chronic hypoxemia (PaO2 less than 55？mmHg (7.3？kPa) or PaO2 ranging from 56 to 59？mmHg (7.4–7.8？kPa) in presence of signs of cor pulmonale, hematocrit > 55%) [13]. The resultant clinical
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