Obesity places a significant load on the respiratory system, affecting lung volumes, respiratory muscle function, work of breathing, and ventilatory control. Despite this, most morbidly obese individuals maintain eucapnia. However, a subgroup of morbidly obese individuals will develop chronic daytime hypercapnia, described as the obesity hypoventilation syndrome (OHS). While obesity is obviously a crucial component of this syndrome, the relationship between excess fat accumulation and the development of awake hypercapnia is complex and extends beyond simply impairments of pulmonary mechanics and lung volumes as a consequence of obesity. Various compensatory mechanisms operate to maintain eucapnia even in the presence of extreme obesity. However, if compensation is impaired, hypoventilation will ensue. While obesity alone does not account for the development of hypoventilation, weight loss will produce significant improvements in lung function and awake gas exchange. Such improvements have the potential to substantially reduce morbidity and mortality in these individuals. Nevertheless, many individuals remain overweight despite substantial weight loss, with persistence of upper airway obstruction. Attention to this residual abnormality is important given the high incidence of cardiovascular abnormalities, including pulmonary hypertension, in individuals with OHS.