Following the classic 'iron lung' non-invasive negative pressure ventilator, non-invasive positive pressure ventilation (NIPPV), particularly used 'nocturnally' has developed a broad role in both the acute hospital setting and domiciliary long-term use for many cardio-respiratory disorders associated with acute and chronic ventilatory failure. This role is based in part upon the perceived relative ease of application and discontinuation of NIPPV, ability to avoid intubation or tracheostomy and their associated morbidities and availability of increasingly portable pressure and volume cycled NIPPV devices. Nevertheless, the many methodologies necessary for optimal NIPPV use are often underappreciated by health care workers and patients alike. This review focuses on the rationale, practice, and future directions for 'nocturnal' use of non-invasive positive pressure ventilation (nNIV) in cardio-respiratory disorders in adults which are commonly associated with sleep-related apnea, hypoventilation and hypoxemia: congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), obesity hypoventilation syndrome (OHS), cystic fibrosis (CF) and neuromuscular disorders.