Itch, or pruritus, is defined as the unpleasant sensation that elicits the desire or reflex to scratch. Chronic itch accompanying cutaneous disease or system disorders affects millions of patients. Itch sensation is detected by the primary sensory neurons in dorsal root ganglia (DRG) which transmit the signals to the central nervous system. The molecular identity of itch-sensing DRG neurons has been a fundamental but puzzling question. Using a combination of mouse genetic tools as well as molecular, cellular, and behavioral approaches, I demonstrated that MrgprA3, a member of the Mas-related G protein-coupled receptors (Mrgprs) family, is a molecular marker to label itch-sensing DRG neurons. Investigation of MrgprA3⁺ DRG neurons provided conceptual advances to the molecular and cellular mechanisms underlying itch sensation and opened new avenues for developing anti-pruritic therapies.