Large fused polycyclic ether natural products of marine origin are some of the most complex and formidable synthetic targets found in Nature, and they continue to fascinate and inspire those engaged in target-directed synthesis and the development of new synthetic methods. Novel strategies for the rapid and stereoselective assembly of fused polyethers have been devised in which ring-closing metathesis reactions are used to accomplish cyclic ether construction. Two-directional and iterative ring construction approaches involving ring-closing metathesis are being employed to assemble polyether sequences found in marine natural products such as the ciguatoxins and gambieric acids.