This editorial is about the roles that TRP channels play in heat and cold sensation and body temperature regulation. These roles may be exploited for therapeutic purposes (indeed, drugs targeting TRPV1, TRPA1 and TRPM8 channels are currently undergoing clinical trials for indications that range from pain through chronic cough and overactive bladder to cancer) or, conversely, may limit drug development (for example, several TRPV1 antagonists were withdrawn from clinical trials due to the hyperthermic reaction that they caused). In the future, modulation of thermosensitive TRP channels may ultimately find application in the treatment not only of pain, but also itch, stroke, asthma, and metabolic disorders. Of the multitude of targets involved in temperature sensation and body temperature regulation, why TRP channels? And why now?