Whipple's disease is a chronic infection caused by Gram-positive bacillus Thropheryma Whippelii picture with a wide range of clinical manifestation, not only systemic but also neurological. Seronegative arthritis or arthralgia may be the only presenting symptom, predating by years gastrointestinal, and also pulmonary, cardiac, renal and neurological manifestations. The diagnosis can be established based on the characteristic histopathological features found in the affected organ (foamy macrophages with a coarsely granular cytoplasm, which stains with PAS) and PCR of 16S ribosomal RNA of Tropheryma Whippelii. CNS involvement manifests with a broad range of neurological symptomatology: memory, consciousness, hypothalamic, psychiatric and behavioural disorders and other symptoms, which may mimic neurodegeneration, neuroinfection, stroke and tumour. In this review detailed neurological symptomatology, differential diagnosis and laboratory, neurophysiologic and radiologic findings are presented. Whipple's disease is potentially fatal but responds to antibiotic treatment. The current recommendations for treatment are discussed.