Obstructive sleep apnea (OSA) has been historically described as a disease primarily of men. However, it is now widely recognized that OSA in women is not as rare as was originally believed. The alarming degree to which OSA is clinically underdiagnosed in women raises the critical concern that women manifest OSA differently. The purpose of this review is to examine the issue of clinically significant gender differences in OSA disease manifestation, which pose unique challenges to diagnosis and management. Within this review, current findings regarding gender differences in OSA polysomnographic features and demographic factors, symptom presentation, functional status, comorbidities, health care utilization, and therapeutic management have been reviewed. Further research in this field is proposed to examine the impact of gender on functional status in individuals with OSA, and the potential gender differences in therapeutic management, particularly the response to continuous positive airway pressure (CPAP) treatment. Additional studies describing the clinical manifestations in men and women at different levels of OSA severity may substantially contribute to the ability to identify and treat OSA in women across a wide spectrum of disease severity.