The depth, rate, and regularity of breathing change following transition from wakefulness to sleep. Interactions between sleep and breathing involve direct effects of the central mechanisms that generate sleep states exerted at multiple respiratory regulatory sites, such as the central respiratory pattern generator, respiratory premotor pathways, and motoneurons that innervate the respiratory pump and upper airway muscles, as well as effects secondary to sleep-related changes in metabolism. This chapter discusses respiratory effects of sleep as they occur under physiologic conditions. Breathing and central respiratory neuronal activities during nonrapid eye movement (NREM) sleep and REM sleep are characterized in relation to activity of central wake-active and sleep-active neurons. Consideration is given to the obstructive sleep apnea syndrome because in this common disorder, state-dependent control of upper airway patency by upper airway muscles attains high significance and recurrent arousals from sleep are triggered by hypercapnic and hypoxic episodes. Selected clinical trials are discussed in which pharmacological interventions targeted transmission in noradrenergic, serotonergic, cholinergic, and other state-dependent pathways identified as mediators of ventilatory changes during sleep. Central pathways for arousals elicited by chemical stimulation of breathing are given special attention for their important role in sleep loss and fragmentation in sleep-related respiratory disorders.