Purpose of review To discuss the role of Clara cell 10-kD protein (CC10), an anti-inflammatory and immunomodulatory molecule, in inflammatory upper airway diseases, particularly in allergic rhinitis and chronic rhinosinusitis (CRS). Recent findings CC10 expression is downregulated in allergic rhinitis and CRS. CC10 can inhibit the expression of chitinase 3-like 1 protein and osteopontin in eosinophilic CRS and allergic rhinitis, respectively. CC10 can also suppress osteopontin-induced expression of Th2 and proinflammatory cytokines in airway epithelial cells, and CC10 gene transfection can inhibit NF-kappa B activity in airway epithelial cells. Proinflammatory and Th2 cytokines can diminish CC10 production, whereas Th1 cytokines and interleukin-10 can promote CC10 production in sinonasal mucosa. Allergen exposure leads to a transdifferentiation of CC10 secreting cells into trefoil factor family 1 secreting cells and/or goblet cells in upper airways, resulting in the diminished expression of CC10. Summary Allergen exposure and Th2 milieu can suppress the expression of CC10 in upper airways. CC10 can inhibit Th2-dominated eosinophilic inflammation in upper airways via multiple pathways.