Among the four G-protein–coupled receptors (H1-H4) identified as the mediators of the biological effects of histamine, the H3 receptor (H3R) is distinguished by its selective expression in the nervous system and its dual function as auto and heteroreceptor that enables H3Rs to modulate the histaminergic and other neurotransmitter systems. The basal ganglia are neuronal nuclei that form a subcortical circuitry responsible for integrating motor and sensory information originated in the cerebral cortex and the thalamus. The abundant presence of H3Rs in the basal ganglia confers these receptors a preferential and strategic position to modulate both the incoming and outgoing synaptic information. In this chapter, we review the control by H3Rs of the release of neurotransmitters involved in the basal ganglia circuitry.