Detection of environmental stimuli that provoke an aversive response has been shown to involve many receptors in the periphery. Probably the least-studied of these stimuli are those that induce the perception of itch (pruritus), an often-experienced unpleasant stimulus. This review covers the ligands and their receptors which are known to cause primary sensory neuron activation and initiate itch sensation. Also covered are several itch-inducing substances which may act indirectly by activating other cell types in the periphery which then signal to primary neurons. Finally, progress in identifying candidate neurotransmitters that sensory neurons use to propagate the itch signal is discussed.