Autoimmune factors are strongly favoured as mediating Guillain-Barré syndrome (GBS); however, the precise mechanisms by which this occurs remain unknown. Microbial infections in a susceptible host resulting in an idiosyncratic immune response which cross-reacts with nerve constituents still remains the most plausible working hypothesis on which much current research is based. Considerable recent evidence indicates that this humoral immune response is at least in part directed to gangliosides. Interestingly, many bacterial toxins, including botulinum and tetanus neurotoxins, also bind to gangliosides and induce diseases with some similarities to GBS. This article discusses the evidence in favour of a pathogenic role for anti-ganglioside antibodies in GBS in the context of our knowledge of the biology of gangliosides and the factors that determine their immunogenicity.