Glutamate is the predominant excitatory neurotransmitter of the basal ganglia, where it acts on ionotropic and metabotropic receptors. In the best studied of the basal ganglia disorders, Parkinson's disease, there is compelling evidence that the activities of glutamatergic pathways are altered. Of particular importance, the glutamatergic subthalamic nucleus becomes overactive. Pharmacologic blockade of subthalamic neurotransmission has antiparkinsonian symptomatic effects and may also help to protect the remaining dopamine neurons of the substantia nigra from excitotoxic neurodegeneration. Development of drugs to manipulate the glutamatergic system with appropriate pharmacologic and anatomic selectivity is likely to dramatically improve our ability to treat disorders of the basal ganglia.