Three patients are described who illustrate distinctive patterns of sleep-disordered breathing that we have observed in patients who are receiving long-term, sustained-release opioid medications. Polysomnography shows respiratory disturbances occur predominantly during non-rapid eye movement (NREM) sleep and are characterized by ataxic breathing, central apneas, sustained hypoxemia, and unusually prolonged obstructive "hypopneas" secondary to delayed arousal responses. In contrast to what is usually observed in subjects with obstructive sleep apnea (OSA), oxygen desaturation is more severe and respiratory disturbances are longer during NREM sleep compared to rapid eye movement sleep. Further studies are needed regarding the effects of opioids on respiration during sleep as well as the importance of interaction with other medications and associated risk factors for OSA.