Recent research has highlighted the important role of the sphenopalatine ganglion (SPG) in cerebrovascular autonomic physiology and in the pathophysiology of cluster and migraine headaches as well as conditions of stroke and cerebral vasospasm. The relatively accessible location of the SPG within the pterygopalatine fossa and the development of options for minimally invasive approaches to the SPG make it an attractive target for neuromodulation approaches. The obvious advantage of SPG stimulation compared to ablative procedures on the SPG such as radiofrequency destruction and stereotactic radiosurgery is its reversibility and adjustable features. The on-going design of strategies for transient and continuous SPG stimulation on as needed basis using implantable SPG stimulators is an exciting new development which is expected to expand the clinical versatility of this technique.