There are a vast number of infectious agents that are associated with gastrointestinal (GI) tract diseases. The epidemiology of GI diseases is changing, with a greater number of conditions increasing in incidence. Challenges exist with establishing cause-and-effect relationships because of the ubiquitous nature of these organisms and the milieu in which they exist. Advances in technology should provide novel methods for identifying and diagnosing these organisms and the relationship they have with a specific digestive disease.