Background: Sphenopalatine ganglion (SPG) blockade or lesioning can offer significant pain relief for cluster headaches (CHs) and a variety of other pain syndromes involving the head and face.; Methods: We reviewed the literature on the efficacy of SPG block and radiofrequency ablation (RFA) using PubMed and Google Scholar.; Results: The infrazygomatic technique can be used to directly access the SPG for injection of local anesthetic or lesioning using RFA. Important technical points to achieve these procedures are described. SPG blockade efficacy is supported by randomized controlled studies but SPG RFA is not.; Conclusion: Targeting the SPG is a promising treatment option for refractory CHs. RFA and neuromodulation have the potential to offer long-term significant pain relief, but more randomized studies are needed to demonstrate their efficacy.