For most patients with obstructive sleep apnea syndrome (OSA), continuous positive airway pressure (CPAP) is an effective therapy. However, for a subset of individuals, CPAP is either not effective or is poorly tolerated. Bilevel positive airway pressure (BPAP) is potentially capable of treating OSA at a lower mean pressure than CPAP and can help augment ventilation via pressure support. This review summarizes the evidence for the use of BPAP in spontaneous mode in the initial treatment of patients with OSA and in those who are poorly compliant with CPAP therapy. It also examines evidence regarding use of BPAP in OSA with associated hypoventilation, such as in chronic obstructive pulmonary disease or severe obesity. Finally, current clinical guidelines that help determine which patients would be candidates for a BPAP device and how to manually titrate BPAP to determine the optimal settings to be prescribed are also discussed.