The respiratory system provides continuous homeostasis of partial pressures of arterial oxygen, carbon dioxide, and pH levels during constantly changing physiologic conditions. This system responds promptly to subtle variations in metabolism. Modifications occur in the regulation and control of respiration with the onset of sleep, which differ with specific sleep stages. These alterations can lead to sleep-related breathing disorders and limit the usual respiratory compensatory changes to specific disease states. This article reviews the normal physiology of respiration in both awake and sleep states, and discusses the effects of common disease processes and medications on the respiratory physiology of sleep.