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Pain is a frequent and poorly treated symptom of Parkinson’s disease, mainly due to scarce knowledge of its basic mechanisms. In Parkinson’s disease, deep brain stimulation of the subthalamic nucleus is a successful treatment of motor symptoms, but also might be effective in treating pain. However, it has been unclear which type of pain may benefit and how neurostimulation of the subthalamic nucleus might interfere with pain processing in Parkinson’s disease. We hypothesized that the subthalamic nucleus may be an effective access point for modulation of neural systems subserving pain perception and processing in Parkinson’s disease. To explore this, we discuss data from human neurophysiological and psychophysical investigations. We review studies demonstrating the clinical efficacy of deep brain stimulation of the subthalamic nucleus for pain relief in Parkinson’s disease. Finally, we present some of the key insights from investigations in animal models, healthy humans and Parkinson’s disease patients into the aberrant neurobiology of pain processing and consider their implications for the pain-relieving effects of subthalamic nucleus neuromodulation. The evidence from clinical and experimental studies supports the hypothesis that altered central processing is critical for pain generation in Parkinson’s disease and that the subthalamic nucleus is a key structure in pain perception and modulation. Future preclinical and clinical research should consider the subthalamic nucleus as an entry point to modulate different types of pain, not only in Parkinson’s disease but also in other neurological conditions associated with abnormal pain processing.