Studies have demonstrated that SPG blockade and neurostimulation can provide pain relief in patients with cluster headaches, migraines, and other trigeminal autonomic cephalalgias. Patients with these conditions showed varying levels and duration of pain relief from SPG blockade. The efficacy of SPG blockade could be related to the different techniques targeting the SPG and choice of therapeutic agents. Based on current studies, SPG blockade is a safe and effective treatment for chronic headaches such as cluster headaches, migraines, and other trigeminal autonomic cephalalgias. Future studies are warranted to define the optimal image-guided technique and choice of pharmacologic agents for SPG blockade as an effective treatment for chronic headaches related to activation of the sphenopalatine ganglion.