Obesity hypoventilation syndrome (OHS) is characterized by obesity, daytime hypercapnia, and sleep-disordered breathing in the absence of other known causes of hypercapnia. Because of the global obesity epidemic and the high prevalence of obstructive sleep apnea in the general population, critical care physicians are likely to encounter patients who have acute-on-chronic respiratory failure attributable to OHS in their clinical practice. In this article we define the clinical characteristics of OHS, review its pathophysiology, and discuss the morbidity and mortality associated with OHS. Finally, we offer treatment strategies during ICU management using noninvasive positive pressure ventilation that may guide the physician in the care of these challenging patients.