Itch is described as an irritating sensation that triggers a desire to scratch. However, this definition hardly seems fitting for the millions of people who suffer from intractable itch. Indeed, the Buddhist philosopher Nāgārjuna more aptly stated, "There is pleasure when an itch is scratched. But to be without an itch is more pleasurable still." Chronic itch is widespread and very difficult to treat. In this review we focus on the molecules, cells and circuits in the peripheral and central nervous systems that drive acute and chronic itch transmission. Understanding the itch circuitry is critical to developing new therapies for this intractable disease.