Clinic-based and epidemiological studies demonstrate a strong association between obesity and obstructive sleep apnea. However, defining the causal relationship between excess body weight and sleep-disordered breathing remains difficult. Potential mechanisms to be considered include: (1) alterations in upper airway structure; (2) alterations in upper airway function; (3) alterations in the balance between ventilatory drive and load and (4) obesity-induced hypoxemia. Additional evidence for the role of obesity in obstructive sleep apnea comes from clinical studies of weight loss in patients with sleep-disordered breathing. Significant weight loss has been reported in most studies, which has been associated with varying degrees of improvement in sleep-disordered breathing, oxygen hemoglobin saturation, sleep architecture and daytime performance. Surgical and nonsurgical approaches to weight loss have been evaluated, although most studies to date suffer from methodological limitations including lack of random assignment to treatment groups, confounding of treatment interventions, absence of untreated controls and lack of adequate follow-up assessment. Implications for research and clinical practice are discussed.