Whipple disease is a rare and potentially fatal bacterial infection induced by a Gram-positive bacillus, Tropheryma whipplei. It is responsible for articular, digestive, neurological, ophthalmological and cardiological symptoms that occur either concomitant or isolated. Thus, the diagnosis is difficult to make and therefore often delayed. A paradoxal exacerbation of the symptoms under immunosuppressive drugs such as glucocorticoids and anti-TNF mAb, or inexpected improvements under antibiotic treatment applied for other reasons should raise a clinicial suspicion of Whipple's disease. Detection of the germ on stool and saliva samples by molecular biology methods has become straightforward with very good positive and negative predictive values. Long-term antibiotic treatment close follow-up are required for the induction of remission and to recognize relapse.