The sphenopalatine ganglion and its involvement in the pathogenesis of pain has been the subject of debate for the last 90 years. The ganglion is a complex neural center composed of sensory, motor, and autonomic nerves, which makes it difficult to determine its pathophysiology. Current indications for blockade of the sphenopalatine ganglion include sphenopalatine and trigeminal neuralgia, migraine and cluster headaches, and atypical facial pain. Methods of blockade use local anesthetics, steroids, phenol, and conventional radiofrequency and electromagnetic field- pulsed radiofrequency lesioning. The techniques for blockade range from superficial to highly invasive. Efficacy studies, though few and small, show promise in patients who have failed pharmacologic or surgical therapies.