Patients with end-stage chronic obstructive pulmonary disease (COPD) frequently develop chronic hypercapnic respiratory failure (CHRF), with disabling symptoms and poor survival. The use of long-term nocturnal non-invasive ventilation (NIV) to treat CHRF in COPD has long been subject of debate due to conflicting evidence. However, since the introduction of high-intensity NIV (HI-NIV) in COPD, physiological and clinical benefits have been shown. HI-NIV refers to specific ventilator settings used for NIV aimed at achieving normocapnia or the lowest partial arterial carbon dioxide pressure (PaCO2 ) values as possible. This review will provide an overview of existing evidence of the efficacy of HI-NIV stable COPD patients with CHRF. Secondly, we will discuss hypotheses underlying NIV benefit in stable hypercapnic COPD, providing insight into better patient selection and hopefully more individually titrated HI-NIV. Finally, we will provide practical advice on how to initiate and follow-up patients on HI-NIV, with special emphasis on monitoring that should be available during the initiation and follow-up of HI-NIV, and will discuss more extended monitoring techniques that could improve HI-NIV treatment in the future.