Objective.-To describe the history of and available data on sphenopalatine ganglion (SPG) neuromodulation in the treatment of headache up to the present. Background.-The SPG has been a therapeutic target to treat primary headache disorders for over 100 years. Multiple destructive lesions have also been tried with variable rate and duration of success. Neurostimulation of the SPG for cluster headache was first described in 2007. Methods.-This is not a systematic review. The authors review the anatomy and pathophysiology of the SPG and cluster headache and the important clinical trials, relating a history of how SPG neuromodulation reached the current state of approval in the European Union (EU) and pivotal registration study for cluster headache in the US. Results.-The EU approved SPG stimulation for cluster headache with a CE Mark in February of 2012. Since then, several EU countries have elected to reimburse implantation for cluster headache, and over 300 patients have been implanted worldwide. Conclusions.-Success rates for implanted SPG neuromodulation in the experimental phase of the European randomized controlled trial, in the open label extension trial, and in the registry of patients implanted outside of the trial remain at about two-thirds of patients implanted being responders, defined as being able to terminate at least 50% of attacks or having at least a 50% decrease in attack frequency or both. A US pivotal registration study is underway to confirm these results and obtain FDA approval for this treatment for cluster headache patients. Further studies in migraine are also underway.