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The American diet is among the safest in the world; however, diseases transmitted by foodborne pathogens (FBPs) still pose a public health hazard. FBPs are the second most frequent cause of all infectious illnesses in the United States. Numerous anecdotal and clinical reports have demonstrated that central nervous system inflammation, infection, and adverse neurological effects occur as complications of foodborne gastroenteritis. Only a few well-controlled clinical or experimental studies, however, have investigated the neuropathogenesis. The full nature and extent of neurological involvement in foodborne illness is therefore unclear. To our knowledge, this review and commentary is the first effort to comprehensively discuss the issue of FBP induced neurotoxicity. We suggest that much of this information supports the role of a theoretical model, the neuro-immune-endocrine system, in organizing and helping to explain the complex pathogenesis of FBP neurotoxicity.