This article examines the headaches that can develop with deep brain stimulation. We identified 15 (23.4%) of 64 patients who developed chronic headaches following implantation of deep brain stimulation electrodes for relief of chronic pain syndromes. Electrodes were implanted in the periaqueductal gray, sensory thalamus, and internal capsule. None of these 15 patients reported similar headaches prior to the implantation. Although 5 patients were intermittent headache sufferers prior to implantation, they reported post-implantation headaches to be completely different in nature. Our experience suggests that headache syndromes may arise due to disturbance of serotonergic neurotransmission within deep brain structures.