Following the introduction of non-invasive positive pressure ventilation (NPPV), the number of patients using home mechanical ventilation has increased substantially and continues to rise worldwide. This is primarily explained by both the effectiveness and comfort that are offered by NPPV in most patients, and particularly in patients with chest wall and neuromuscular diseases. For clinically stable patients the qualification for NPPV largely depends on the presence of complaints or signs of (nocturnal) hypoventilation with accompanying hypercapnia. For patients who are referred by an ICU there are additional prerequisites. In any case, the aims of NPPV should be met and NPPV should be effective. The initiation of NPPV, whether in the clinic or not, should always be tailored to the individual patient. Based on effectiveness, safety, and comfort, the best ventilator has to be chosen. Although with modern interfaces NPPV may be provided continuously, for continuing NPPV over the years, adding manual and/or mechanical cough augmentation techniques is usually mandatory. To control the ongoing effectiveness of NPPV regular monitoring of the patient is essential, and nowadays transcutaneous measurement of CO2 seems the most reliable and appropriate technique. For trend analysis, downloaded data of modern ventilators may be helpful as well. The ultimate goal of NPPV, to prevent tracheotomy, can only be reached if the patient has continuous access to a centre with expertise in cough augmentation techniques and both nocturnal and diurnal NPPV.