The striatum is a nodal structure of the basal ganglia circuits and is one of the brain areas with the highest concentration of markers of cholinergic transmission. Giant aspiny cholinergic interneurons constitute only 1%–3% of the neurons of the striatum but exert a powerful influence on its output, which is mediated by the medium spiny neurons (MSNs). Acetylcholine (ACh), acting via different receptor subtypes, affects the activity of the MSNs both directly and via modulation of glutamate release from corticostriate terminals and of dopamine release from nigrostriatal terminals. Acetylcholine, via its reciprocal interactions with dopamine (DA), has an important role in the differential modulation of striatal output via the so-called direct and indirect pathways of the basal ganglia circuits. Recent evidence indicates that ACh release in the striatum, triggered by thalamic inputs, provides a “stop” signal that interrupts ongoing motor behavior in response to salient stimuli from the environment. Cholinergic mechanisms in the striatum may contribute to the pathophysiology of Parkinson disease (PD) and dystonia, and may have a beneficial role in Tourette syndrome and other stereotypies. The physiology of cholinergic interneurons and the effects of ACh in the striatum recently have been reviewed. 1–4