Taste receptors on the tongue communicate information to the brain about the nutrient content or potential toxicity of ingested foods. However, recent research has now shown that taste receptors are also expressed far beyond the tongue, from the airway and gastrointestinal epithelia to the pancreas and brain. The functions of many of these so-called extraoral taste receptors remain unknown, but emerging basic science and clinical evidence suggests that bitter and sweet taste receptors in the airway are important in sensing bacteria and regulating innate immunity. This review focuses on the role of bitter and sweet taste receptors in human airway innate immunity and the potential clinical relevance to airway infections. The T2R38 bitter taste receptor in sinonasal cilia detects bitter bacterial quorum-sensing molecules and activates nitric oxide-dependent innate immune responses. Polymorphisms that underlie T2R38 functionality also appear to be involved in susceptibility to upper respiratory infection and chronic rhinosinusitis (CRS). Bitter and sweet receptors in specialized sinonasal solitary chemosensory cells control antimicrobial peptide secretion, which may have important implications for airway infections in CRS patients as well as patients with diabetes mellitus. Future research on taste receptors in the airway has tremendous potential to identify immune mechanisms involved in host-pathogen interactions and thus reveal novel therapeutic targets.