G protein-coupled receptors (GPCRs) play a central role in regulating the functions of a diverse range of cell types in the airway. Taste 2 receptor (T2R) family of GPCRs is responsible for the transduction of bitter taste; however, recent studies have demonstrated that different subtypes of T2Rs and key components of T2R signaling are expressed in several extra-oral tissues including airways with many physiological roles. In the lung, expression of T2Rs has been confirmed in multiple airway cell types including airway smooth muscle (ASM) cells, various epithelial cell subtypes, and on both resident and migratory immune cells. Most importantly, activation of T2Rs with a variety of putative agonists elicits unique signaling in ASM and specialized airway epithelial cells resulting in the inhibition of ASM contraction and proliferation, promotion of ciliary motility, and innate immune response in chemosensory airway epithelial cells. Here we discuss the expression of T2Rs and the mechanistic basis of their function in the structural cells of the airways with some useful insights on immune cells in the context of allergic asthma and other upper airway inflammatory disorders. Emphasis on T2R biology and pharmacology in airway cells has an ulterior goal of exploiting T2Rs for therapeutic benefit in obstructive airway diseases.