Chemosensing at brain barriers is crucial for brain health and homeostasis. The mechanisms and molecules involved in the chemosensing processes are indisputable gatekeepers of the central nervous system, which detect the composition of the peripheral and brain fluids to trigger detoxification and elimination of noxious compounds, prevent their entrance in the central nervous system, or expel them to the circulation, if resulting from the brain metabolism. These systems encompass the tightness of brain endothelial cells at the blood–brain barrier and choroid plexus epithelial cells at the blood–cerebrospinal fluid barrier which prevent paracellular movement of molecules, detoxification enzymes, and efflux transporters, among others. More recently, the detection of taste and olfactory receptors at brain barriers added another important group of players to these systems: receptors, which bind an enormous variety of compounds and trigger cellular responses which can promote or prevent the uptake of such compounds. This chapter focuses on taste receptors at brain barriers and their potential to enable or prevent the entrance of compounds into the brain.