Several controversial neurotoxic syndromes have received notoriety in the past several decades. For each, the controversy involves the most fundamental question about the existence of the disorder as a clinically diagnosable entity. Interestingly, the most controversial of these syndromes share several features, including argument about the existence of each syndrome in the courtroom. The authors focus their discussion on three problems (painter's encephalopathy, silicone breast implant neurotoxicity, and the Gulf War syndrome) for which no scientific consensus has been reached that would establish them as diagnosable disorders. These syndromes do not meet traditional disease criteria, and until a clear set of symptoms and objective signs can be defined, a definite course and clear cause demonstrated, and specific tests and treatments identified, these syndromes are likely to remain highly controversial.