Trigeminal neuralgia is a severe chronic disorder that causes paroxysmal pain and dramatically decreases the quality of life of its patients. Although the pathophysiology of this disease has been extensively studied, the underlying molecular processes are still unclear, especially the role of voltage-dependent sodium channels in the triggering of painful crises. The main objective of this review is to summarize and update the important role of voltage-dependent sodium channels in the pathophysiology of trigeminal neuralgia, emphasizing the structural, functional and genetic alterations of these channels. It is concluded that trigeminal neuralgia is related to both congenital and acquired alterations in the e xpression of various voltage-dependent sodium channel isoforms.