Whipple’s disease is a chronic multiorgan infection caused by Tropheryma whipplei, a weakly staining gram-positive bacillus. Humans are the only known host. Seroprevalence studies indicate that ∼50% of people in Western Europe and ∼75% of those in rural Senegal have been exposed to T. whipplei, and the disease prevalence is estimated at 1–3 cases per 1 million population. The route of transmission is unclear but probably involves fecal–oral spread and possibly involves droplet and/or airborne transmission.