The cranial rhythmic impulse is a palpable, rhythmic fluctuation believed to be synchronous with the primary respiratory mechanism. The precise physiologic mechanism of the cranial rhythmic impulse is not fully understood. Based on traditional and current views of the cranial rhythmic impulse, animal studies, and clinical findings in patients with chronic fatigue syndrome, the author argues that the cranial rhythmic impulse is the rhythm produced by a combination of cerebrospinal fluid drainage from the neuraxis (brain and spinal cord) and pulsations of central lymphatic drainage induced by the sympathetic nervous system. In addition, evidence is provided to demonstrate that a disturbed, palpable, and visible neurolymphatic process leads to chronic fatigue syndrome. This process may also explain the pathophysiologic mechanisms leading to other disease states. Finally, the author’s proposed manual treatment protocol for patients with chronic fatigue syndrome is described.