Whipple's disease is a chronic, multisystem disease that is caused by Tropheryma whippelii infection. More information is now known about this unusual infectious process, which was once considered uniformly fatal. Immunologic, diagnostic, and therapeutic advancements are reviewed in this article. Hopefully, future advances in the basic and clinical sciences will lead to a more rapid diagnosis, more complete understanding of the effects of infection, improved therapy, and better clinical outcome.