Publisher Summary Guillain-Barre syndrome (GBS) is a postinfectious polyradiculoneuropathy. Molecular mimicry between microbial structures and glycolipids (gangliosides) on peripheral nervous tissue is thought to elicit a ganglioside-specific immune response, resulting in localized inflammation and tissue damage. Although experimental evidence supports a role for anti-ganglioside antibodies in GBS pathogenesis, the mechanisms, which eventually trigger the production of cross-reactive antibodies in a small percentage of individuals, have remained elusive. Gangliosides are sialic acid-containing glycolipid structures, consisting of a hydrophobic ceramide moiety, anchored in the cell membrane, and linked to externally exposed hydrophilic carbohydrate structures. Host and pathogen characteristics, which contribute to the development of this monophasic autoimmune disorder, remain to be identified. This chapter aims at providing an overview of the role of anti-ganglioside antibodies in the pathogenesis of GBS, as well as describing the possible interaction of pathogens with the immune system, leading to an induction of pathogenic antibodies.