Evaluation of the upper airway is key for a successful surgical management. Proper evaluation can be done only with a good understanding of the anatomy and pathophysiology of the upper airway. The authors discuss surgical anatomy from a soft tissue and bony perspective in detail along with its clinical implications. The complex interaction among pharyngeal dilator tone, arousal threshold, respiratory control instability, and changes in lung volume during sleep play an important role in obstructive sleep apnea. Because all the anatomic and physiologic characteristics discussed have genetic predisposition, gene therapy may play a pivotal role in the future.