Sensory receptors across the entire tongue are engaged during eating. However, the tongue has distinctive regions with taste (fungiform and circumvallate) and non-taste (filiform) organs that are composed of specialized epithelia, connective tissues, and innervation. The tissue regions and papillae are adapted in form and function for taste and somatosensation associated with eating. It follows that homeostasis and regeneration of distinctive papillae and taste buds with particular functional roles require tailored molecular pathways. Nonetheless, in the chemosensory field, generalizations are often made between mechanisms that regulate anterior tongue fungiform and posterior circumvallate taste papillae, without a clear distinction that highlights the singular taste cell types and receptors in the papillae. We compare and contrast signaling regulation in the tongue and emphasize the Hedgehog pathway and antagonists as prime examples of signaling differences in anterior and posterior taste and non-taste papillae. Only with more attention to the roles and regulatory signals for different taste cells in distinct tongue regions can optimal treatments for taste dysfunctions be designed. In summary, if tissues are studied from one tongue region only, with associated specialized gustatory and non-gustatory organs, an incomplete and potentially misleading picture will emerge of how lingual sensory systems are involved in eating and altered in disease.