Acute itch (pruritus) is unpleasant and acts as an alerting mechanism for removing irritants. However, severe chronic itch is debilitating and impairs the quality of life. Rapid progress has been made in recent years in our understanding of the fundamental neurobiology of itch. Notably, several temperature-sensitive transient receptor potential (thermo-TRP) ion channels have emerged as critical players in many types of itch, in addition to pain. They serve as markers that define the itch neural pathway. Thermo-TRP ion channels are thus becoming attractive targets for developing effective anti-pruritic therapies.