Clostridium difficile was originally reported as an agent of enteric disease in 1977.Subsequent work has shown this organism to be what many consider the most important bacterial pathogen of the gut in developed countries in terms of severity of disease and prevalence. A review of the literature indicates that almost all of the clinically relevant data for this organism were reported by 1981, including data on the spectrum of disease, clinical settings in which it is suspect, epidemiology, pathophysiologic mechanisms, distinction between toxin A and toxin B,diagnostic tests, and therapeutic guidelines. This report reviews the historical data that led to the discovery of C. difficile, current information that is clinically relevant, and remaining issues of concern as a guide for future studies.