Home mechanical ventilation (HMV) is an effective long-term treatment for chronic hypercapnic respiratory failure. In addition to the established practice of providing HMV for the treatment of chronic ventilatory failure in slowly progressive neuromuscular and chest wall disease, there is accumulating evidence for improvement of quality of life and prolongation of survival by HMV in highly prevalent diseases like chronic obstructive pulmonary disease and ever-increasing obesity hypoventilation syndrome as well as rapidly progressive neuromuscular disease. The key concepts for successful HMV are an experienced team selecting the right patients, timely initiation of adequate ventilation via an appropriate interface, and monitoring effectiveness during regular long-term follow-up. Coaching of patients with chronic respiratory failure on long-term HMV within a dedicated service and collaborations with community services for home care are essential. The current review describes various important practical aspects of HMV that remain frontiers in the implementation of the current knowledge in clinical practice and may help in providing effective HMV to all those in need.