Gambierol was isolated as a neurotoxin from the cultured cells of the ciguatera causative dinoflagellate Gambierdiscus toxicus and classified as a member of the polycyclic ether family of marine toxins. The structure consists of a ladder-shaped trans-fused octacyclic ring system that includes 18 stereogenic centers, two 1,3-diaxial dimethyl-substituted tetrahydropyranyl rings, and a partially conjugated triene side chain. The total synthesis of gambierol has been achieved by utilizing an oxiranyl anion strategy in an iterative manner. Synthetic highlights of this route include direct carbon-carbon formation on epoxides, sulfonyl-assisted 6-endo cyclization, and an expansion reaction of the tetrahydropyranyl rings to oxepanes to forge the polycyclic architecture of the target molecule.