Evaluation of health-related quality of life (HRQL) has become steadily more essential during the last two decades in research and health care practice in order to evaluate the human and financial costs and benefits of modern medical techniques. HRQL in its definition is based on different components of health including physical state, psychological well-being, social relations and functional capacities that are influenced by a persons experience, beliefs, expectations, and perceptions. For the purpose of assessment of HRQL several instruments have been developed. Generic instruments are not specific to any particular disease and are therefore most commonly used for general survey research on health allowing comparisons between disease states. In contrast, disease-specific questionnaires which are necessary in order to focus on domains most relevant to a particular disease are thought to be more sensitive than generic instruments following therapeutic interventions. Home mechanical ventilation (HMV) delivered noninvasively by a facial mask is a well established treatment for chronic hypercapnic respiratory failure. It is widely accepted that survival improves following institution of HMV in most patients with chest wall deformities or neuromuscular diseases while this is still controversially discussed in patients with COPD. However, patients receiving HMV usually have severe respiratory insufficiency with a past medical history of several years or decades, and suffer from end stage disease with objectively severe limitations of daily living. In addition, HMV is a time consuming and cost intensive therapy. Therefore, several studies have been conducted in the last decade to evaluate HRQL in patients receiving HMV. Recent studies using generic questionnaires have shown impairments in HRQL in patients receiving HMV compared to normals. This was primarily attributed to severe limitations in physical health, but not in mental health indicating that if severe physical limitation occurs in advanced respiratory disease this will not necessarily lead to mental limitation. In addition, limitations in HRQL in patients with HMV were not substantially higher than in patients with different chronic disease being not dependent on HMV. Improvements in HRQL following the institution of HMV were only mild or even insignificant in patients with COPD, but patients with restrictive ventilatory disorders are suspected to have more benefits. However, well validated disease-specific questionnaires which are designed to be more sensitive in the assessment of changes in HRQL than generic instruments have been introduced recently for patients with severe respiratory failure, but the influence of HMV to HRQL remains still unclear, since prospective studies using these questionnaires have yet not been finished.