Whipple’s disease (WD), first described by George Hoyt Whipple in 1907, is a rare chronic multi-systemic infectious disorder caused by the Gram-positive bacillus, Tropheryma whipplei. 1, 2 Infection may involve any organ in the body, and most commonly affects white men in the fourth to sixth decades of life. The pathogenesis of WD is unknown but host-linked factors are known to be present. The presence of interleukin (IL)-4 inside the phagocytes seems to be important. Patients with WD show signs of altered cell immunity before and after treatment. The typical clinical manifestations of classical WD are arthralgia, weight loss, diarrhea, and abdominal pain. 2-5 Some patients present with migratory arthralgia of the large joints or, less often, with a nondeforming oligoarthritis or polyarthritis, which may precede the onset of typical gastrointestinal symptoms by an average of 8 years. The main gastrointestinal manifestations of the disease are diarrhea, weight loss, and malabsorption, which may progress to a severe wasting syndrome and abdominal lymphadenopathy. The most common ocular manifestations are those secondary to the involvement of the CNS and include nystagmus, ophthalmoplegia, and palpebral ptosis, among others. Patients can present with bilateral panuveitis and retinal vasculitis. Both anterior chamber inflammation and moderate vitritis are present. Upper gastrointestinal endoscopy of the small intestine is still the first diagnostic test of choice. Duodenal biopsies are histologically characterized by foamy macrophages in the lamina propria. The determination of the nucleotide sequence of the 16S rRNA gene of T. whipplei enabled the development of polymerase chain reaction systems with a high sensitivity and specificity. The therapeutic goal in all patients with WD is to eradicate the infection and to avoid relapses. Co-trimoxazole is often used as the drug of first choice, because of its ability to penetrate the uninflamed blood-brain barrier. The likelihood of neurological relapse is less after the use of cotrimoxazole than with other antibiotic regimens, such as tetracycline and the combination of penicillin and streptomycin.