Gangliosides, N-acetylneuraminic acid (sialic acid)-bearing glycosphingolipids, are believed to reside in clusters within membrane microdomains, called lipid rafts or glycosynapse. Recent studies demonstrated that antiganglioside antibodies play an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). The anti-GM1 antibodies are likely to damage peripheral nerves through complement activation with dysfunction of voltage-gated sodium channels. Some antiganglioside antibodies may cause dysfunction of voltage-gated calcium channels without complement activation. Clustered epitopes of ganglioside complexes (GSCs) consisting of two gangliosides can be targeted by serum antibodies in GBS and FS. Anti-GD1a/GD1b complex antibodies are associated with severe GBS. Approximately 50% of FS patients have antibodies to GSCs containing GQ1b or GT1a. Various glycolipids including GSCs may form complex glycolipid environment in the cell membrane, regulating the accessibility and the avidity of antiganglioside antibodies. In addition to antibody specificity, the glycolipid environment or specific distribution of target gangliosides in peripheral nervous system can influence pathogenic effects of antiganglioside antibodies in GBS and FS. Conformational and functional analyses of glycoepitopes of GSCs in the biological membrane will provide new vistas to research on antibody-antigen interaction in GBS, and shed light on microdomain function mediated by carbohydrate-to-carbohydrate interaction.