Continuous positive airway pressure (CPAP) remains the major treatment option for obstructive sleep apnea (OSA). The American Thoracic Society organized a workshop to discuss the importance of mask selection for OSA treatment with CPAP. In this workshop report, we summarize available evidence about the breathing route during nasal and oronasal CPAP and the importance of nasal symptoms for CPAP outcomes. We explore the mechanisms of air leaks during CPAP treatment and possible alternatives for leak control. The impact of nasal and oronasal CPAP on adherence, residual apnea–hypopnea index, unintentional leaks, and pressure requirements are also compared. Finally, recommendations for patient and partner involvement in mask selection are presented, and future directions to promote personalized mask selection are discussed.