Obstructive sleep apnea (OSA) is a multifactorial condition, and an interdisciplinary approach to diagnosis forms the basis for effective treatment planning. Craniofacial structure and attached soft tissues and muscles play a central role in OSA. Evidence-based studies demonstrate the effectiveness of oral appliances for mandibular advancement and tongue stabilization in managing OSA, and current clinical standards of practice recommend the use of oral appliances to treat OSA when patients cannot tolerate continuous positive airway pressure (CPAP). Although effective, oral appliances are less predictable in managing OSA compared with CPAP therapy. Measures can be taken to improve predictability of oral appliance treatment.