Whipple's disease is a rare chronic infectious disorder first described in 1907 by G.H. Whipple. The disorder is caused by the newly identified bacterium Tropheryma whipplei and there is evidence that altered immune functions play a role in the manifestation of the disease. The organ systems mostly affected are the joints and the gut, and in the further course often also the heart, lung, brain, and eyes. The intestinal involvement occurs with abdominal pain and diarrhea, which leads to weight loss, malnutrition, and anemia. In some cases the infection spreads to the central nervous system, which may lead to loss of memory, confusion, or disturbances in gait. In the last few years, several steps towards an improved diagnosis of the disease and characterization of the causative bacterium have been made. While untreated disease may be lethal, treatment is often able to eradicate the organism. At present, therapy is based on observations in small patient groups and personal experience. There are different antibiotic therapy regimens often starting with intravenous application for 2 weeks followed by oral medication for 1 year. The first clinical therapy study is ongoing.