Obesity hypoventilation syndrome (OHS) consists of a combination of obesity and chronic hypercapnia accompanied by sleep-disordered breathing. During the last 3 decades, the prevalence of extreme obesity has markedly increased in the United States and other countries. With a global epidemic of obesity, the prevalence of OHS is bound to increase. Patients with OHS have a lower quality of life with increased health-care expenses and are at a higher risk for the development of pulmonary hypertension and early mortality compared to eucapnic patients with sleep-disordered breathing. Despite the significant morbidity and mortality associated with this syndrome, it is often unrecognized and treatment is frequently delayed. Clinicians must maintain a high index of suspicion since early recognition and treatment reduces the high burden of morbidity and mortality associated with this syndrome. In this review, we will discuss the definition and clinical presentation of OHS, provide a summary of its prevalence, review the current understanding of the pathophysiology, and discuss the recent advances in the therapeutic options.