The nose and upper airway play a sentinel role in the respiratory tract, alerting an individual to the qualities of the inspired atmosphere. The upper airway also clears contaminants from the inspired airstream and physically conditions inspired air before its entry into the lower respiratory tract. Given these anatomical and functional considerations, the nose may be the initial-or even prime-target of air pollutants. This article reviews the functional anatomy of the upper airway in humans, its vulnerabilities to various classes of air contaminants, and the relationship between chemical irritation and allergic inflammation in the upper airway.