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Clostridium difficile is a Gram-positive, rod-shaped, motile, spore forming, obligate anaerobe, which is part of the gastrointestinal flora of man and animals. Some strains of C. difficile produce toxins and are capable of causing mild-to-severe diarrhea and pseudomembranous colitis. Further, C. difficile has been found to be a common cause of nosocomial antibiotic-associated diarrhea and is the most frequent cause of infectious diarrhea in hospitals and long-term care facilities globally. It is the only nosocomially significant anaerobic bacterium that forms spores (which are hard to destroy), though C. difficile may also be present as a colonizing inhabitant of the normal gut microbiota of some individuals and yet produce no visible signs of disease. Most cases of C. difficile infection occur in patients who are prescribed high-dose antibiotics or prescribed antibiotics for a prolonged period of time. These antibiotics can disturb the normal balance of the gut microbiota, altering its composition and allowing the overgrowth of C. difficile bacteria. When this occurs, the C. difficile bacteria produce toxins, which can damage gut tissues and cause diarrhea. This mini review discusses the epidemiology, history, role of antibiotics and virulence factors associated with C. difficile infections.