Whipple's disease is a systemic infection, caused by the bacterium Tropheryma whipplei, with protean clinical manifestations characterized by fever, weight loss, diarrhea, polyarthritis, skin hyperpigmentation and adenopathy. For a long time, due to the inability to culture the causative organism, diagnosis was based on histologic examination of infected tissues, usually duodenal biopsies, which revealed diastase-resistant periodic acid-Schiff-positive staining. Now, PCR of various tissues or fluid is emerging as a way to diagnose Whipple's disease. However, the presence of T. whipplei DNA in saliva, gastric juice or duodenal biopsies of healthy individuals has led to questions regarding the specificity of the molecular techniques involved. After a series of failures, stable culture was achieved in 2000. Subsequently, the generation of rabbit polyclonal antibodies has led to the detection of the bacterium in tissues by immunohistology. However, culture and immunohistology are very recent techniques and are not yet widely used. Propagation of the bacterium will lead to extensive molecular knowledge of T. whipplei, which will help in the diagnosis and understanding of the epidemiology and pathogenicity of Whipple's disease.