The Guillain-Barré syndrome (GBS) represents the prototypic immune-mediated peripheral neuropathy, which is now recognized as a group of conditions with diverse pathology and pathogenesis. The observation that plasma exchange and intravenous immunoglobulin result in clinical improvement, the presence of circulating antibodies targeting structures on peripheral nerve tissue in sera from GBS patients, and the deposition of immunoglobulins and complement demonstrated on myelinated fibers in nerve biopsies from affected patients point to a critical role of the humoral immune response in the pathogenesis of GBS. However, the observation of inflammatory infiltrates in nerve and the critical pathogenic role of neuritogenic T lymphocytes as demonstrated in the animal model support the concept that a disordered cellular immunity is also of critical importance in the pathogenesis of this neuropathy. Current treatment strategies are aimed at mitigating the harmful effects of the immune system on peripheral nerve. This review will address the rationale for immunotherapy in GBS based on experimental and immunologic studies of the pathogenesis of this disease.