The detection of temperature is one of the most fundamental sensory functions across all species, and is critical for animal survival. Animals have thus evolved a diversity of thermosensory mechanisms allowing them to sense and respond to temperature changes (thermoreception). A key process underlying thermoreception is the translation of thermal energy into electrical signals, a process mediated by thermal sensors (thermoreceptors) that are sensitive to a specific range of temperatures. In disease conditions, the temperature sensitivity of thermoreceptors is altered, leading to abnormal temperature sensation such as heat hyperalgesia. Therefore, the identification of thermal sensors and understanding their functions and regulation hold great potential for developing novel therapeutics against many medical conditions such as pain.