This review deals with clinical features of multiple system atrophy (MSA), especially on natural history, sleep disordered breathing, and nocturnal sudden death, based on our recent analyses of definite MSA which we experienced in our institute. Fiberoptic laryngoscopic examination performed under propofol anesthesia revealed that upper airway obstruction is caused not only by vocal cord abductor paralysis but also by various mechanisms including floppy epiglottis and stenosis at the arytenoids during inspiration. We must be cautious not to exacerbate upper airway obstruction by continuous positive airway pressure (CPAP), which is now increasingly used to treat sleep disordered breathing of MSA. Our analyses also demonstrated that nocturnal sudden death was the most frequent cause of death in our MSA cohort, and CPAP could not be a prophylactic measure against sudden death. In order to prevent nocturnal sudden death, a new project is now under way using non-invasive positive airway pressure ventilation (NPPV) and/or artificial ventilation associated with tracheostomy.