Over the past 20 years, deep brain stimulation (DBS) has evolved to become an important part of the clinical management strategy in patients with Parkinson’s disease (PD) who develop altered responses to drugs or drug-induced adverse effects, particularly prolonged or variable off-time and drug-resistant tremor, as well as drug-induced dyskinesias. Following the discovery of the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in humans [1], the MPTP-induced, experimental, non-human primate model of PD was soon developed. Studies on this model established that the loss of nigro-striatal dopamine results in disinhibition of the subthalamic nucleus (STN). This, in turn, leads to excitation of the globus pallidus internus (GPi) with subsequent inhibition of the motor thalamus and brain stem. This could explain the bradykinesia, rigidity, posture, and gait dysfunction in PD. The primate MPTP model therefore predicted that lesioning the STN would ameliorate parkinsonian symptoms, and this was subsequently established by ibotenate and radiofrequency lesions of the STN, first in the monkey model [2], and then in the clinic [3]. Following this, it was discovered that high-frequency stimulation of the STN in a PD model in the rat had the same effects as lesioning [4]. STN-DBS surgery has now become the intervention of choice in advanced PD when drug treatment is not adequately effective [5].