Itch is an unpleasant somatic sensation with the desire to scratch, and it consists of sensory, affective, and motivational components. Acute itch serves as a critical protective mechanism because an itch-evoked scratching response will help to remove harmful substances invading the skin. Recently, exciting progress has been made in deciphering the mechanisms of itch at both the peripheral nervous system and the CNS levels. Key neuronal subtypes and circuits have been revealed for ascending transmission and the descending modulation of itch.