In many disease states, alveolar hypoventilation initially manifests during sleep before development of chronic hypercapnia during wakefulness. Alveolar hypoventilation, defined by increased P_aCO₂, occurs due to reduced minute ventilation and/or increased dead space. While mild alveolar hypoventilation may occur during sleep in healthy subjects, hypoventilation is accentuated in disease states with potential carryover to the daytime producing chronic hypercapnia. Maintenance of eucapnia during wakefulness requires compensatory mechanisms that are dependent upon intact integration between respiratory mechanics, respiratory control and acid-base regulatory systems. This review characterizes the disease states based on pathophysiologic derangements and focuses on the compensatory regulatory mechanisms.