Since the first device for mechanical emergency ventilation was introduced in 1907, there have been substantial changes with regard to technical advances on the one hand and indications and outcome targets on the other. The rationale for implementation of mechanical ventilation has gradually been amended. Initially, the primary goal was to merely safeguard survival in emergency cases; in recent years, the goal of long-term ventilation with primary outcome of survival has been gradually shifted to patient’s quality of life, especially where ventilation may last for months, years or even decades. For long-term ventilation, the impact on patient’s quality of life may be diverse and a fine-tuned discussion on pros and cons may be primarily driven by the question of securing quality of life under mechanical ventilation. In general, doctors and families underestimate the patients’ quality of life. In neurology in industrialized countries, ventilation is regarded a standard therapy for progressive neurodegenerative diseases, such as amyotrophic lateral sclerosis and spinal muscular atrophy, and neuromuscular diseases, for instance, Duchenne muscular dystrophy. This chapter reviews our current understanding of quality of life under long-term mechanical ventilation and discusses controversies.